Bacteria and Viruses

Barron’s Chapter 10

PART I: Bacteria and archaea

Prokaryote structure

Watch “Bacteria”

Watch “Prokaryotic and eukaryotic cells”

Read: “Prokaryote structure”

Key points:
• Prokaryotes are single-celled organisms belonging to the domains Bacteria and Archaea.
•
• Prokaryotic cells are much smaller than eukaryotic cells, have no nucleus, and lack organelles.
•
• All prokaryotic cells are encased by a cell wall. Many also have a capsule or slime layer made of
polysaccharide.
•
• Prokaryotes often have appendages (protrusions) on their surface. Flagella and some pili are used for
locomotion, fimbriae help the cell stick to a surface, and sex pili are used for DNA exchange.
•
• Most prokaryotic cells have a single circular chromosome. They may also have smaller pieces of circular
DNA called plasmids.

Introduction
Bacteria often get a bad rap: they’re described as unsafe “bugs” that cause disease. Although some types
of bacteria do cause disease (as you know if you've ever been prescribed antibiotics), many other are
harmless, or even beneficial.

Bacteria are classified as prokaryotes, along with another group of single-celled organisms, the archaea.
Prokaryotes are tiny, but in a very real sense, they dominate the Earth. They live nearly everywhere – on
every surface, on land and in water, and even inside of our bodies.

To emphasize that last point: you probably have about the same number of prokaryotic cells in your body
as human cells! That may sound gross, but many of our prokaryotic "sidekicks" play important roles in
keeping us healthy.

In this article, we'll look at what prokaryotes are and what exactly makes them different from eukaryotes
(such as you, a houseplant, or a fungus). Then, we'll take a closer look at the structures these efficient,
omnipresent little organisms use to survive.

What are prokaryotes?

Prokaryotes are microscopic organisms belonging to the domains Bacteria and Archaea, which are two out
of the three major domains of life. (Eukarya, the third, contains all eukaryotes, including animals, plants,
and fungi.) Bacteria and archaea are single-celled, while most eukaryotes are multicellular.

Fossils show that prokaryotes were already here on Earth 3.5 billion years ago, and scientists think that
prokaryotic ancestors gave rise to all of the life forms present on Earth today.

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 Prokaryotes vs. eukaryotes
Prokaryotes and eukaryotes are similar in some fundamental ways, reflecting their shared evolutionary
ancestry. For instance, both you and the bacteria in your gut decode genes into proteins
through transcription and translation. Similarly, you and your prokaryotic inhabitants both pass genetic
information on to your offspring in the form of DNA.

In other ways, prokaryotes and eukaryotes are quite different. That may be obvious when we're comparing
humans to bacteria. But for me at least, it's less obvious when we're comparing a bacterium to a yeast
(which is tiny and unicellular, but eukaryotic). What actually separates these categories of organisms?

The most fundamental differences between prokaryotes and eukaryotes relate to how their cells are set
up. Specifically:

• Eukaryotic cells have a nucleus, a membrane-bound chamber where DNA is stored, while prokaryotic cells
don't. This is the feature that formally separates the two groups.
•
• Eukaryotes usually have other membrane-bound organelles in addition to the nucleus, while prokaryotes
don't.
•
• Cells in general are small, but prokaryotic cells are really small. Typical prokaryotic cells range from 0.2 -
2 µm in diameter, while typical eukaryotic cells range from 10 - 100 µm in diameter.
•
Many prokaryotic cells have sphere, rod, or spiral shapes (as shown below). In the following sections, we’ll
walk through the structure of a prokaryotic cell, starting on the outside and moving towards the inside of
the cell.

Prokaryotic cells are typically shaped as either spheres (called cocci), rods (called bacilli), or spirals.

The capsule
Many prokaryotes have a sticky outermost layer called the capsule, which is usually made of
polysaccharides (sugar polymers).

The capsule helps prokaryotes cling to each other and to various surfaces in their environment, and also
helps prevent the cell from drying out. In the case of disease-causing prokaryotes that have colonized the
body of a host organism, the capsule or slime layer may also protect against the host’s immune system.

Remember Griffith's experiment, which demonstrated the existence of a "transforming principle" (DNA)
that could turn rough, harmless bacteria into smooth, pathogenic bacteria? The smooth bacteria were
smooth (and capable of causing disease) because they had a capsule!

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The cell wall
All prokaryotic cells have a stiff cell wall, located underneath the capsule (if there is one). This structure
maintains the cell’s shape, protects the cell interior, and prevents the cell from bursting when it takes up
water.

The cell wall of most bacteria contains peptidoglycan, a polymer of linked sugars and polypeptides.
Peptidoglycan is unusual in that it contains not only L-amino acids, the type normally used to make
proteins, but also D-amino acids ("mirror images" of the L-amino acids). Archaeal cell walls don't contain
peptidoglycan, but some include a similar molecule called pseudopeptidoglycan, while others are
composed of proteins or other types of polymers.

Don’t plants have a cell wall too?

Some eukaryotes, such as plants and fungi, also have cell walls, but they are made of different materials
than those of prokaryotes. Plant cell walls are made primarily of cellulose, and fungal cell walls are made
of a modified polysaccharide called chitin. You can learn more about cellulose and chitin in the article on
carbohydrates.

The external structures of the prokaryotic cell include a plasma membrane, cell wall, and capsule (or
slime layer).

Some of the antibiotics used to treat bacterial infections in humans and other animals act by targeting the
bacterial cell wall. For instance, some antibiotics contain D-amino acids similar to those used in
peptidoglycan synthesis, "faking out" the enzymes that build the bacterial cell wall (but not affecting
human cells, which don't have a cell wall or utilize D-amino acids to make polypeptides).

Gram staining

A gram stain depicting both, gram-positive bacteria (violet) and gram-negative bacteria (pink).
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Although most bacterial cell walls contain peptidoglycan, they can differ in other ways. In fact, these
differences are used to classify bacteria using a technique called the Gram stain. Developed by the 19th-
century Danish physician Christian Gram, this technique categorizes strains of bacteria into one of two
groups: gram-positive or gram-negative.

The staining process involves applying two dyes to a sample of bacteria. First, a violet dye and iodine are
applied, which bind together and form a bulky molecule in the cell walls of the bacteria. Alcohol is then
used to wash the sample, removing leftover or loosely bound violet dye-iodine complexes, and a red dye
is applied to the sample.

The structure of the cell wall of the bacteria determines which dye is visible at the end of the procedure.
Gram-positive bacteria have a thick cell wall of peptidoglycan, which traps the bulky violet dye-iodine
molecules. (The red dye also binds, but the violet dye covers it up.) Gram-negative bacteria, on the other
hand, have a thin layer of peptidoglycan and an additional outer membrane (see image below). The thin
peptidoglycan layer only retains the red dye, giving gram-negative bacteria a pinkish hue.

Gram-positive bacteria have an inner plasma membrane and a thick cell wall composed of peptidoglycan.
Gram-negative bacteria have an inner plasma membrane and a thin cell wall composed of peptidoglycan
and an outer membrane.

The plasma membrane

Underneath the cell wall lies the plasma membrane. The basic building block of the plasma membrane is
the phospholipid, a lipid composed of a glycerol molecule attached a hydrophilic (water-attracting)
phosphate head and to two hydrophobic (water-repelling) fatty acid tails. The phospholipids of a
eukaryotic or bacterial membrane are organized into two layers, forming a structure called
a phospholipid bilayer.

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 Structure of a phospholipid, showing hydrophobic fatty acid tails and hydrophilic head (including ester
linkages, glycerol backbone, phosphate group, and attached R group on phosphate group). A bilayered
membrane consisting of phospholipids arranged in two layers, with their heads pointing out and their
tails sandwiched in the middle, is also shown.

The plasma membranes of archaea have some unique properties, different from those of both bacteria
and eukaryotes. For instance, in some species, the opposing phospholipid tails are joined into a single tail,
forming a monolayer instead of a bilayer (as shown below). This modification may stabilize the membrane
at high temperatures, allowing the archaea live happily in boiling hot springs.

The plasma membrane of bacterial and eukaryotic (and some archael) cells is composed of a phospholipid
bilayer. The tails of opposite-facing phospholipids remain separated, forming two separate layers.
The plasma membrane of some archaeal cells is composed of a phospholipid monolayer. The tails of
opposite-facing phospholipids become united, forming a single layer.

Appendages
Prokaryotic cells often have appendages (protrusions from the cell surface) that allow the cell to stick to
surfaces, move around, or transfer DNA to other cells.

Thin filaments called fimbriae (singular: fimbria), like those shown in the picture below, are used for
adhesion—that is, they help cells stick to objects and surfaces in their environment.

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A fimbria (plural: fimbriae) is a type of appendage of prokaryotic cells. These hair-like protrusions allow
prokaryotes to stick to surfaces in their environment and to each other.

Longer appendages, called pili (singular: pilus), come in several types that have different roles. For
instance, a sex pilus holds two bacterial cells together and allows DNA to be transferred between them in
a process called conjugation. Another class of bacterial pili, called type IV pili, help the bacterium move
around its environment.

The most common appendages used for getting around, however, are flagella (singular: flagellum). These
tail-like structures whip around like propellers to move cells through watery environments.

Bacteria may have various types of surface structures. These include fimbriae, short protrusions found all
over the surface of the bacterium; a flagellum, found at the back of the bacterium and used for
propulsion; and a sex pilus, used to grab on to other bacteria for exchange of genetic material.

Chromosome and plasmids

Most prokaryotes have a single circular chromosome, and thus a single copy of their genetic material.
Eukaryotes like humans, in contrast, tend to have multiple rod-shaped chromosomes and two copies of
their genetic material (on homologous chromosomes).

Also, prokaryotic genomes are generally much smaller than eukaryotic genomes. For instance, the E.
coli genome is less than half the size of the genome of yeast (a simple, single-celled eukaryote), and
almost 700 times smaller than the human genome!

By definition, prokaryotes lack a membrane-bound nucleus to hold their chromosomes. Instead, the
chromosome of a prokaryote is found in a part of the cytoplasm called a nucleoid.

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 Prokaryotes generally have a single circular chromosome that occupies a region of the cytoplasm called a
nucleoid. They also may contain small rings of double-stranded extra-chromosomal DNA called plasmids.

In addition to the chromosome, many prokaryotes have plasmids, which are small rings of double-
stranded extra-chromosomal ("outside the chromosome") DNA. Plasmids carry a small number of non-
essential genes and are copied independently of the chromosome inside the cell. They can be transferred
to other prokaryotes in a population, sometimes spreading genes that are beneficial to survival.

For instance, some plasmids carry genes that make bacteria resistant to antibiotics. (These genes are
called R genes.) When the plasmids carrying R genes are exchanged in a population, they can quickly
make the population resistant to antibiotic drugs. While beneficial to the bacteria, this process can make
it difficult for doctors to treat harmful bacterial infections.

Internal compartments
Prokaryotes aren't "supposed" to have internal compartments like the organelles of eukaryotes, and for
the most part, they don't. However, prokaryotic cells sometimes need to increase membrane surface area
for reactions or concentrate a substrate around its enzyme, just like eukaryotic cells. Because of this,
some prokaryotes have membrane folds or compartments functionally similar to those of eukaryotes.

For example, photosynthetic bacteria often have extensive membrane folds to increase surface area for
the light-dependent reactions, similar to the thylakoid membranes of a plant cell. These bacteria may
also have carboxysomes, protein-enclosed cellular compartments where carbon dioxide is concentrated
for fixation in the Calvin cycle.

Check your understanding!

1. You are looking at a recently discovered unicellular organism using a powerful microscope.
How can you determine if the organism is a prokaryote or eukaryote?
Choose 1 answer:
o (Choice A) It is unicellular, so it must be a prokaryote
o (Choice B) If it has membrane infoldings for photosynthesis, it must be a eukaryote
o (Choice C) If it has a cell wall, it must be a prokaryote
o (Choice D) If it has a membrane-bound nucleus, it must be a eukaryote

Read: “Prokaryote reproduction and biotechnology”

Key points:
• Prokaryotes (bacteria and archaea) reproduce asexually through binary fission. Most prokaryotes
reproduce rapidly.
•
• Due to their fast growth and simple genetics, E. coli bacteria are widely used in molecular biology.
•

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• In the laboratory, a gene can be transferred into E. coli bacteria on a small, circular DNA molecule called
a plasmid. The plasmid is taken up by the bacteria in a process called transformation.
•
• The transformed E. coli bacteria can be used to make many copies of the plasmid. In some cases, they
will also express the gene on the plasmid and make protein.

Introduction
Let's say you have one bacterium. How can you get more identical bacteria? How quickly can you get
them? And, most importantly, why on Earth would you want a whole bunch of identical bacteria?

Let's fast-forward to that last question: some bacteria, most notably Escherichia coli (E.coli), are widely
used in molecular biology labs. There, they serve as little "factories" that churn out many copies of a
desired DNA molecule, or many molecules of a needed protein (such as the insulin used by diabetics to
regulate their blood sugar). The more bacteria, the more of the DNA or protein product that can be made.

Two features that make E. coli very useful in the lab are its rapid reproduction and its generation of
clones, or genetically identical bacteria. Let's take a quick look at how E. coli and other prokaryotes
reproduce. Then, we'll examine their applications in biotechnology.

How do prokaryotes reproduce?

Prokaryotes reproduce through a cell division process called binary fission. Like mitosis in eukaryotes,
this process involves copying the chromosome and separating one cell into two.

Binary fission is an asexual form of reproduction, meaning that it does not involve production of eggs and
sperm or mixing of genetic material from two individuals. Except in the case of rare mutations, or
changes in DNA sequence, binary fission produces daughter cells that are genetically identical to the
mother cell.

You can learn more about the steps of binary fission in the binary fission article in the cell division
section.

Prokaryotes reproduce fast!

Prokaryotes in general reproduce much faster than multicellular eukaryotes. This can be measured in
terms of generation time, or the length of time from the birth of one generation to the birth of the next.

For humans, a typical generation time might be in the neighborhood of 20 years. For a typical bacterium,
that might be closer to 20 minutes! As a matter of fact, the E. coli bacteria that live inside your gut, and
that are widely used in laboratory research, can produce a new generation every 17 minutes or so.

Not all bacteria are quite this quick, and some pathogenic ones, such as Mycobacterium tuberculosis,
have a generation time over 12 hours. Still, prokaryotes in general are fast multipliers, which means their
populations can grow very rapidly—in a natural environment, or, in some cases, in a test tube in the lab.

Bacteria in molecular biology

Bacteria that reproduce quickly and are easy to grow in the lab make good model organisms for many
scientific studies. E. coli, for instance, is one of the most widely used organisms in biological research.

Although you may have heard of E. coli as a food contaminant, harmless strains of E. coli are used in
biology labs worldwide. In fact, many basic biological processes, like the mechanism of DNA replication,
were first discovered in E. coli.

E. coli as DNA and protein factories

Today, E. coli are sometimes used as tiny “factories” to synthesize DNA or proteins. Researchers can
insert a gene of interest into E. coli cells through a process called transformation (uptake of DNA from
the environment), which is described further in the article on prokaryote genetic variation. In such
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experiments, the gene of interest is typically borne on a piece of circular DNA called a plasmid, which can
be copied by the bacterium and passed on to its offspring.

Plasmid for bacterial transformation. It is a circular DNA molecule that contains a target gene (such as
insulin, in the case of recombinant insulin production), a promoter used to drive expression of the gene,
and an antibiotic resistance gene.

Once they contain the plasmid with the gene of interest, the E. coli cells will replicate it and pass it along
each time they divide, making many copies of the plasmid DNA. If the plasmid contains the right control
sequences, the E. coli can also be instructed to transcribe and translate the gene of interest, producing
protein. For example, most of the insulin used by diabetics is produced in E. coli cells using this strategy.

Steps of transformation
In a typical transformation experiment, the target gene (blue DNA above) is first inserted into a plasmid.
In addition to the target gene, the plasmid also contains a gene that provides resistance to a particular
antibiotic (red DNA above). If the goal is to use the bacteria to synthesize protein from the gene, the
plasmid will also contain a promoter, or control sequence, that allows the target gene to be expressed in
bacteria (green DNA above).

When copies of the plasmid are mixed with E. coli cells and the cells are heat-shocked (exposed briefly to
high temperature), a small fraction of them will take up the plasmid. All of the E. coli are then spread on
a nutrient plate containing the antibiotic. The purpose of the antibiotic is to only let bacteria with the
plasmid survive and grow.

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 Steps of bacterial transformation.
1. Plasmid is added to bacteria.
2. Heat shock triggers bacteria to take up plasmid. Most don't take up the plasmid, but a few do.
3. All of the bacteria are placed on an antibiotic plate.
4. Only the bacteria with the plasmid can survive. Each one reproduces to make a colony.
5. A colony is grown up to make many more identical bacteria. The bacteria are induced to make the target
protein such as insulin.

E. coli lacking the plasmid will be killed by the antibiotic. E. coli that contain the plasmid, however, can
survive and reproduce (thanks to the antibiotic resistance gene in the plasmid). Each resistant cell will
form a colony of genetically identical bacteria, which appears on the agar plate as small dot. An
antibiotic-resistant colony can be analyzed (checked by other methods to confirm it contains the correct
plasmid), then grown up to make a large culture of identical, plasmid-bearing bacteria.

What use is a large culture of plasmid-bearing bacteria? Sometimes, researchers need many copies of the
plasmid DNA for use in another experiment, and they can extract this DNA from the culture. Alternatively,
if the plasmid contains the right promoter, the bacteria can be induced (instructed) to express the gene
and synthesize protein. This technique is used to produce some medically important proteins, such as
insulin and human growth hormone.

Read: “Genetic variation in prokaryotes”

Key points:
• In transformation, a bacterium takes up a piece of DNA floating in its environment.
•
• In transduction, DNA is accidentally moved from one bacterium to another by a virus.
•
• In conjugation, DNA is transferred between bacteria through a tube between cells.
•
• Transposable elements are chunks of DNA that "jump" from one place to another. They can move
bacterial genes that give bacteria antibiotic resistance or make them disease-causing.

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Introduction
When you hear the word "clone," what do you think of? Maybe Dolly the sheep, or experiments carried out
in molecular biology labs. But it's also true that the bacteria around you—on your skin, in your gut,
growing on your kitchen sink—are "cloning" themselves all the time!

Bacteria reproduce by splitting in two via binary fission. Binary fission makes clones, or genetically
identical copies, of the parent bacterium. Since the "child" bacteria are genetically identical to the
parent, binary fission doesn't provide an opportunity for genetic recombination or genetic diversity (aside
from the occasional random mutation). This contrasts with sexual reproduction.

Still, genetic variation is key to the survival of a species, allowing groups to adapt to changes in their
environment by natural selection. That's true for bacteria as well as plants and animals. So it's not too
surprising that prokaryotes can share genes by three other mechanisms: conjugation, transformation, and
transduction.

Transformation
In transformation, a bacterium takes in DNA from its environment, often DNA that's been shed by other
bacteria. In a laboratory, the DNA may be introduced by scientists (see biotechnology article). If the DNA
is in the form of a circular DNA called a plasmid, it can be copied in the receiving cell and passed on to its
descendants.

Left: plasmid taken up by transformation.

Right: linear DNA fragment taken up by transformation and swapped into the bacterial chromosome by
homologous recombination.

Why would this be important? Imagine that a harmless bacterium takes up DNA for a toxin gene from a
pathogenic (disease-causing) species of bacterium. If the receiving cell incorporates the new DNA into its
own chromosome (which can happen by a process called homologous recombination), it too may become
pathogenic.

Transduction
In transduction, viruses that infect bacteria move short pieces of chromosomal DNA from one bacterium
to another "by accident."

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Yep, even bacteria can get a virus! The viruses that infect bacteria are called bacteriophages.
Bacteriophages, like other viruses, are the pirates of the biological world—they commandeer a cell's
resources and use them to make more bacteriophages.

However, this process can be a little sloppy. Sometimes, chunks of host cell DNA get caught inside the
new bacteriophage as they are made. When one of these "defective" bacteriophages infects a cell, it
transfers the DNA. Some bacteriophages chop the DNA of their host cell into pieces, making this transfer
process more likely.

Virus infects cell by injecting its DNA. Bacterial DNA is fragmented and viral DNA is replicated. New viral
particles are made and exit the cell. One contains host DNA instead of viral DNA. When this virus infects
a new host, it injects the bacterial DNA, which can recombine with the chromosome of the new host.

Archaea, the other group of prokaryotes besides bacteria, are not infected by bacteriophages but have
their own viruses that move genetic material from one individual to another.

Conjugation
In conjugation, DNA is transferred from one bacterium to another. After the donor cell pulls itself close
to the recipient using a structure called a pilus, DNA is transferred between cells. In most cases, this DNA
is in the form of a plasmid.

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1. An F+ donor cell contains its chromosomal DNA and an F plasmid. It has a rodlike pilus. A recipient F- cell
has only a chromosome and no F plasmid.
2. The donor cell uses its pilus to attach to the recipient cell, and the two cells are pulled together.
3. A channel forms between the cytoplasms of the two cells, and a single strand of the F plasmid is fed
through.
4. Both of the cells now have an F plasmid and are F+. The former recipient cell is now a new donor and can
form a pilus.

Donor cells typically act as donors because they have a chunk of DNA called the fertility factor (or F
factor). This chunk of DNA codes for the proteins that make up the sex pilus. It also contains a special site
where DNA transfer during conjugation begins.

If the F factor is transferred during conjugation, the receiving cell turns into an F+ donor that can make
its own pilus and transfer DNA to other cells. Here's one analogy: this process is sort of like how a vampire
can turn other people into vampires by biting them.

Transposable elements
Transposable elements are also important in bacterial genetics. These chunks of DNA "jump" from one
place to another within a genome, cutting and pasting themselves or inserting copies of themselves in
new spots. Transposable elements are found in many organisms (including you and me!), not just in
bacteria.

In bacteria, transposable elements sometimes carry antibiotic resistance and pathogenicity genes (genes
that make bacteria disease-causing). If one of these transposable elements "jumps" from the chromosome
into a plasmid, the genes it carries can be easily passed to other bacteria by transformation or
conjugation. That means the genes can spread quickly through the population.

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 One way that transposons can move around the genome is by copying themselves and inserting the copy
into a new location. In this diagram, a transposon in the bacterial chromosome is copied and inserts into
a plasmid.

Conclusion
In bacteria, reproduction can be very fast, with a generation taking little more than a few minutes for
some species. This short generation time, together with random mutations and the mechanisms of genetic
recombination we saw in this article, allow bacteria (and other prokaryotes) to evolve very quickly.

Is that a good thing? It depends on your perspective. Rapid evolution means that bacteria can adapt to
environmental changes, such as the introduction of an antibiotic, very quickly. That's good for them—but
bad for us, when we are the ones with the infection!

Check your understanding

1. Match each type of gene transfer with its definition.
Type of transfer Description
• A bacterial cell takes up DNA from its environment
• Conjugation • One bacterium transfers DNA to another bacterium to
• Transformation which it's physically connected
• Transduction • A virus moves DNA from one bacterial cell to another

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 Prokaryote metabolism and ecology

Read: “Prokaryote metabolism”

Key points:
• Some prokaryotes are phototrophs, getting energy from the sun. Others are chemotrophs, getting energy
from chemical compounds.
•
• Some prokaryotes are autotrophs, fixing carbon from CO2. Others are heterotrophs, getting carbon from
organic compounds of other organisms.
•
• Prokaryotes may perform aerobic (oxygen-requiring) or anaerobic (non-oxygen-based) metabolism, and
some can switch between these modes.
•
• Some prokaryotes have special enzymes and pathways that let them metabolize nitrogen- or sulfur-
containing compounds.
•
• Prokaryotes play key roles in the cycling of nutrients through ecosystems.

Introduction
In the scheme of things, you and I have a fairly limited range of ways to feed ourselves. We may get to
decide between veggies and ice cream (and hopefully, end up enjoying both in healthy quantities!).
However, it's not too likely that we're going to photosynthesize. We're also unlikely to eat hydrogen
sulfide, the compound responsible for "rotten egg smell," for breakfast.

Prokaryotes (bacteria and archaea) are way more diverse than humans in their nutritional strategies – that
is, the ways they obtain fixed carbon (fuel molecules) and energy. Some species consume organic material
like dead plants and animals. Others live off of inorganic compounds in rocks. One bacterium, Thiobacillus
concretivorans, consumes metal-melting sulfuric acid!

In this article, we will take a closer look at the many ways that prokaryotes obtain and metabolize food,
and how they can influence cycling of nutrients.

Nutritional modes
All of Earth’s life forms need energy and fixed carbon (carbon incorporated into organic molecules) to
build the macromolecules that make up their cells. This applies to humans, plants, fungi, and, of course,
prokaryotes. Living organisms can be categorized by how they obtain energy and carbon.

First, we can categorize organisms by where they get fixed (usable) carbon:
•
• Organisms that fix carbon from carbon dioxide (CO2) or other inorganic compounds are called autotrophs.
•
• Organisms that get fixed carbon from organic compounds made by other organisms (by eating the
organisms or their by-products) are called heterotrophs.

In addition, we can categorize organisms by where they get energy:

•
• Organisms that use the light (mainly the sun) as a source of energy are called phototrophs.
•
• Organisms that use chemicals as a source of energy are called chemotrophs.

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 We can divide prokaryotes (and other organisms) into four different categories based on their energy and
carbon sources:
Nutritional mode Energy source Carbon source
Photoautotroph Light Carbon dioxide (or related compounds)
Photoheterotroph Light Organic compounds
Chemoautotroph Chemical compounds Carbon dioxide (or related compounds)
Chemoheterotroph Chemical compounds Organic compounds

We tend to be pretty familiar with photoautotrophs, such as plants, and chemoheterotrophs, such as
humans and other animals. Prokaryote species fall into these two categories, as well as the two less
familiar categories (photoheterotrophs and chemoautotrophs) to which plants and animals don't belong.

Aerobic and anaerobic respiration

Another metabolic area in which prokaryotes differ from humans (and are much more diverse than us!) is
their need for oxygen. Some need it, some are poisoned by it, and some can take it or leave it depending
on availability.

• Prokaryotes that need O2 in order to metabolize are called obligate aerobes. Humans are also obligate
aerobes (as you've found out if you've tried to hold your breath for too long).
•
• Prokaryotes that can't tolerate O2 and only perform anaerobic metabolism are called obligate
anaerobes. C. botulinum, the bacterium that causes botulism (a form of food poisoning) when it grows in
canned food, is an obligate anaerobe – which is why it multiplies well inside of sealed cans.
•
• Facultative anaerobes use aerobic metabolism when O2 is present, but switch to anaerobic metabolism if
it's absent. The bacteria that cause staph and strep infections are examples of facultative anaerobes.

Sulfur and nitrogen metabolism

Some bacteria and archaea have metabolic pathways that allow them to metabolize nitrogen and sulfur in
ways that eukaryotes cannot. In some cases, they use nitrogen- or sulfur-containing molecules to obtain
energy, but in other cases, they expend energy to convert these molecules from one form to another.

Sulfur metabolism
Some fascinating examples of sulfur-metabolizing prokaryotes are found in deep-sea ecosystems. For
instance, certain prokaryotic species can oxidize hydrogen sulfide (H2S) from piping hot hydrothermal
vents. They use energy released in this process to fix inorganic carbon from the water into sugars and
other organic molecules in a process called chemosynthesis.

Sulfur-metabolizing prokaryotes form the basis of food chains in their deep-sea habitats (where not the
tiniest ray of light can reach to support photosynthesis). The sulfur metabolizers support entire
communities of organisms, including worms, crabs, and shrimp, thousands of meters below the ocean
surface.

Nitrogen metabolism
Nitrogen-metabolizing prokaryotes include nitrogen fixers, nitrifiers, and denitrifiers. They play key roles
in the nitrogen cycle by converting nitrogen compounds from one chemical form to another.

Nitrogen-fixing prokaryotes convert (“fix”) atmospheric nitrogen (N2) into ammonia (NH3), which plants
and other organisms can incorporate into organic molecules. Some plant species in the legume family,
such as peas, form mutually beneficial relationships (mutualisms) with nitrogen-fixing bacteria. The
plants house and feed the bacteria in structures called root nodules, and the bacteria provide fixed
nitrogen to the roots.
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Other prokaryotes in the soil, called nitrifying bacteria, convert the ammonia into other types of
compounds (nitrates and nitrites), which may also be absorbed by plants. Denitrifying prokaryotes do
more or less the reverse, turning nitrates into N2 gas.

Biogeochemical cycles
The constant recycling of chemical elements is vital to the functioning of ecosystems. In
Earth's biogeochemical cycles, chemical elements are converted among various different forms in a
repeating cycle.

By virtue of their diverse metabolisms, prokaryotes play important roles in many global cycles. Here, we'll
take a closer look at their function in two of these: the nitrogen and carbon cycles.

Nitrogen cycle
As we saw in the last section, nitrogen-fixing prokaryotes convert (“fix”) atmospheric nitrogen (N2) into
ammonia (NH3). Plants and other organisms can then use the ammonia to build molecules such as amino
acids and nucleotides.

Other prokaryotes in the soil, the nitrifying bacteria, convert ammonia into other types of compounds
(nitrates and nitrites), which may also be absorbed by plants. The denitrifying prokaryotes, which convert
nitrates into N2, move nitrogen atoms from the soil back to the atmosphere.

The image below shows a simplified version of the nitrogen cycle, emphasizing the roles of prokaryotes.

Prokaryotes play several roles in the nitrogen cycle. Nitrogen-fixing bacteria (in the soil and within the
root nodules of some plants) convert nitrogen gas in the atmosphere to ammonia. Nitrifying bacteria
convert ammonia to nitrites or nitrates. Ammonia, nitrites, and nitrates are all fixed nitrogen and can be
absorbed by plants. Denitrifying bacteria converts nitrates back to nitrogen gas.

17
 Carbon cycle
Prokaryotes are also important in the carbon cycle. Photosynthetic prokaryotes, such as cyanobacteria,
use light energy to remove CO2 from the atmosphere and fix it into organic molecules. This is the same
basic process carried out by photosynthetic plants.

Prokaryotic decomposers, on the other hand, move carbon in the opposite direction. When they break
down dead organic material (from previously living plants and animals), they return CO2 to the
atmosphere via cellular respiration. Decomposition also releases a variety of other elements and inorganic
molecules for reuse.

The image below shows a simplified version of the carbon cycle, emphasizing the roles of prokaryotes.

Prokaryotes play several roles in the carbon cycle. Decomposing prokaryotes break down dead organic
matter and release carbon dioxide through cellular respiration. Photosynthetic prokaryotes remove
atmospheric carbon dioxide and fix it into sugars.

Check your understanding!

1. Which of the following statements about metabolic strategies of bacteria are true?
True False
Some bacteria conduct photosynthesis and produce oxygen, much like plants.
Bacteria are always autotrophic but they may get energy from either light or chemical
sources.
Some chemosynthetic bacteria introduce energy and fixed carbon into communities
where photosynthesis is not possible (e.g., deep-sea vents).
Some bacteria live symbiotically inside of host organisms and provide the host with
nutrients.

18
 Read: “Prokaryote interactions & ecology”

Key points:
• Bacteria can be highly cooperative. Some even form organized structures a lot like a multicellular tissue.
•
• Biofilms are surface-attached collections of microorganisms that stick together and exchange nutrients.
•
• Some prokaryotes form close associations with plants, animals, or fungi. These may
be mutualisms (+/+), commensalisms (+/0), or parasitisms (+/-).

Bacteria: Surprisingly interactive!

If I say bacteria, what's the first word that comes to mind? Odds are, it probably isn't cooperative.
However, bacteria and other prokaryotes (archaea) are proving to be social and cooperative, much more
so than biologists first thought.

Some bacteria cooperate in groups, dividing up metabolic tasks and sharing the products. Others form
cooperative associations with a host organism (though some also form neutral or harmful associations).

In this article, we will first explore how bacteria cooperate with each other and form organized groups
(sometimes almost seeming “multicellular”). Then, we’ll look at some of the ways they interact with
other species.

Cooperation and “multicellularity” in bacteria

Bacteria often benefit from cooperating with each other. This cooperation can be loose, or it can be
coordinated to the point where it starts to look very much like eukaryotic multicellularity!

Here are some examples of bacterial cooperation – you can judge for yourself whether they really count
as multicellular or not (an ongoing and controversial question in biology).

Myxobacteria
Myxobacteria are soil bacteria that interact to form coordinated groups (and even complex structures
with specialized cells). When lots of resources are available, myxobacteria form groups called swarms. A
swarm moves in a coordinated way and feeds by secreting digestive enzymes into the soil and absorbing
the digested material.

The myxobacteria, Myxococcus xanthus, form fruiting bodies (yellow sac-like structures) when resources
are scarce. The fruiting bodies contain long-lasting myxospores that will germinate when resources
become available again, reforming a swarm.

If resources become scarce, the myxobacteria join together to form multicellular-like structures
called fruiting bodies (see the image above). Within fruiting bodies, cells mature into spore-like
structures called myxospores. Each myxospore has a thick cell wall than enables it to persist over a long
period of time. When resources become available, the myxospores germinate and a new swarm is
produced.

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Chain-forming cyanobacteria
Cyanobacteria in the genus Anabaena don't split off on their own when they're produced by binary fission
(bacterial cell division). Instead, they stick together in chains of connected cells, as shown in the image
below.

The cyanobacteria, Anabaenaform interconnected chains of two cell types: photosynthetic cells and
heterocysts. The former only produce sugars and the latter only fix nitrogen. All of the cells in a chain
share their metabolic products with each other.

The cyanobacterial cells have the capacity to both photosynthesize and fix nitrogen. However, a single
cell can't do both at once, because the oxygen released in photosynthesis blocks nitrogen fixation (impairs
the nitrogen-fixing enzymes).

To get around this issue, when nitrogen availability in the environment is low, some of the cells in the
chain will become cells called heterocysts. The heterocysts specialize in fixing nitrogen, unlike the rest of
the cells in the chain, which carry out photosynthesis.

Biofilms
A biofilm is a surface-attached collection of microorganisms held together by a gooey substance (mostly
carbohydrate) that they secrete themselves. In many cases, biofilms form via quorum sensing. In quorum
sensing, bacteria continually exchange signals that allow them to detect population density, and they
change their behavior when density exceeds a certain threshold.

Biofilms often contain multiple types of bacteria or other microorganisms. In some cases, the different
members of the biofilm are metabolically complementary, with one producing molecules the other can
use. Biofilms typically have water-permeable channels for exchange of nutrients and wastes, and some
biologists compare them to a "primitive circulatory system."

Most bacteria in nature probably live on surfaces, rather than being free-floating, and biofilms are all
quite literally everywhere. They form on household surfaces, such as kitchen counters, cutting boards,
sinks, and toilets. Even plaque scraped off your teeth by dentists is a biofilm!

20
 A biofilm of Staphylococcus aureus bacteria. The biofilm consists of cells stuck together by a
polysaccharide matrix.

Biofilms often get the most attention when they're causing problems. Pathogenic (disease-causing)
biofilms, such as the Staphylococcus biofilm pictured above, can be a serious problem in hospitals. They
are often hard to kill with antibiotics, and they can cause persistent infections if they contaminate
medical equipment, such as catheters. Other biofilms corrode metal pipes and damage industrial
equipment.

Some biofilms, however, have beneficial applications. For example, biofilms are used in water treatment
plants to remove organic matter from sewage.

Multicellular or not?
In the examples above, bacteria interact cooperatively. To some degree, the social behavior of cells in a
biofilm is analogous to the cooperation of cells in a multicellular organism. Anabaena and myxobacteria
are, in my opinion at least, even closer to multicellular.

Some scientists argue that these cooperative bacteria qualify as multicellular organisms. Others, however,
say that prokaryotes can't really be multicellular, and that these are just groups of individuals cooperating
(for example, like ants in an anthill). The jury is still out, so you get to be the judge!

Mutualistic, commensal, and parasitic bacteria

We just saw some special cases where bacteria interact to form organized (dare we say multicellular?)
associations. However, many types of bacteria also form close relationships with eukaryotic species such
as humans, often living inside them.

Three important types of ecological interactions between species are mutualism, commensalism, and
parasitism. Bacteria can participate in all three types of interactions. In fact, we humans encounter lots
of bacteria in each category!

Mutualism
Some bacteria form mutualisms, mutually beneficial (+/+) relationships between two organisms.

For example, Ruminococcus bacteria live in the gut of a cow and break down cellulose, a carbohydrate
from grass, into a form usable by the cow. Without these bacteria, cows could not digest the grass they
eat! In return, the bacteria get nutrients and a safe place to live (the gut of the cow).

Commensalism
Bacteria can also form commensalisms, relationships where one partner benefits and the other is not
affected (+/0).

21
 For example, we humans have millions of bacteria living in and on our bodies, many of which are thought
to have a commensal relationship with us (for instance, feeding on dead cells or metabolic by-products).
However, it's often the case that these commensal relationships actually turn out to be slightly
mutualistic or parasitic (see below) when they are examined carefully.

Parasitism
A parasitism is a relationship where one organism benefits and the other is hurt (+/-). Parasitic bacteria
are the ones that we humans are most familiar with, and the ones that give bacteria their bad reputation
as nasty "bugs."

The bacteria that cause human diseases take resources from the human body and also attack the host in
other ways, producing the nasty symptoms of a bacterial infection.

Parasites may harm their host in a variety of ways, such as invading tissues, producing toxins, or causing
direct damage to host cells. Some parasites, such as the Toxoplasma gondii that cause toxoplasmosis,
even get directly inside the cells of their host.

Check your understanding!

1. Myxobacteria are soil bacteria that generally live together in a cooperative group called a swarm.
When resources become scarce, individual myxobacteria merge to make a fruiting body, a multicellular
structure that allows some cells to mature into spores (specialized structures with thick cell walls that
can withstand difficult conditions). When conditions again become favorable, these spores germinate to
form a new swarm.

How might forming a fruiting body help myxobacteria populations survive?

Choose all answers that apply:
o (Choice A) By ensuring that at least some members of the group survive (as spores) until resources become
available
o (Choice B) By allowing some myxobacteria to disperse from the group, decreasing competition for
resources
o (Choice C) By ensuring that when conditions are again favorable, a group of myxobacteria will germinate,
allowing the population to resume group-living behaviors
o (Choice D) By generating fruit that the myxobacteria can eat

Read: “Prokaryote classification and diversity”

Key points:
• The two prokaryote domains, Bacteria and Archaea, split from each other early in the evolution of life.
•
• Bacteria are very diverse, ranging from disease-causing pathogens to beneficial photosynthesizers and
symbionts.
•
• Archaea are also diverse, but none are pathogenic and many live in extreme environments.
•
• A DNA sequencing approach called metagenomics lets scientists identify new species of bacteria and
archaea, including ones that can't be cultured.

Introduction
Prokaryotes, which include both bacteria and archaea, are found almost everywhere – in every ecosystem,
on every surface of our homes, and inside of our bodies! Some live in environments too extreme for other
organisms, such as hot vents on the ocean floor.

22
Although they are found all around us, prokaryotes can be hard to detect, count, and classify. The
prokaryotic species we know of today are a tiny fraction of all prokaryotic species thought to exist. In
fact, the very idea of a “species” becomes complicated in the world of prokaryotes!

In this article, we'll first look at major groups of prokaryotes. Then, we'll explore why it’s often tricky to
identify and classify them. Finally, we'll see how DNA sequencing methods are helping us get a better
picture of the prokaryotes around us.

A prokaryote "family tree"

For a long time, all prokaryotes were classified into a single domain (the largest taxonomic grouping).

However, work by microbiologist Carl Woese in the 1970s showed that prokaryotes are divided into two
distinct lineages, or lines of descent: Archaea and Bacteria. Today, these groups are considered to form
two out of three domains of life. The third domain (Eukarya) includes all eukaryotes, such as plants,
animals, and fungi.

This phylogeny (evolutionary tree) depicts the evolutionary relationships between the three domains of
life: Eukarya, Archaea, and Bacteria. The two prokaryotic domains (Archaea and Bacteria) each comprise
several smaller taxonomic groupings. Within the Archaea are the euryarchaeotes, crenarchaeotes,
nanoarchaeotes, and korarchaeotes. Within the Bacteria are proteobacteria, chlamydias, spirochetes,
cyanobacteria, and gram-positive bacteria.

Since splitting off from one another millions of years ago, both Bacteria and Archaea have split off into
many groups and species.

Bacteria
Domain Bacteria contains 5 major groups: proteobacteria, chlamydias, spirochetes, cyanobacteria, and
gram-positive bacteria.

23
The proteobacteria are subdivided into five groups, alpha through epsilon. Species in these groups have a
wide range of lifestyles. Some are symbiotic with plants, others live in hot vents deep under the sea, and
others yet cause human diseases, such as stomach ulcers (Helicobacter pylori) and food poisoning
(Salmonella).

24
The other four major groups of bacteria are similarly diverse. Chlamydias are pathogens that live inside
host cells, while cyanobacteria are photosynthesizers that make much of Earth's oxygen. Spirochetes
include both harmless bacteria and harmful ones, like the Borrelia burgdorferi that cause Lyme disease.
The same is true of Gram-positive bacteria, which range from probiotic bacteria in yogurt to the Bacillus
anthracis that cause anthrax.

Chlamydia, Spirochetes, Cyanobacteria, and Gram-positive bacteria are described in this table.

25
Archaea
Domain Archaea contains 4 major groups. Intriguingly, so far, no archaea that are human pathogens have
yet been discovered.

Archaea do live in our bodies and those of animals—for instance, in the gut—but all of them seem to be
harmless or beneficial. Although there are hypotheses, no one yet knows exactly why archaea are all
"friendly," i.e., why no disease-causing species have evolved.

Alongside the archaea that enjoy the comfy environment of the human gut, there are
many extremophile species that live in much more inhospitable places. These include volcanic hot
springs, undersea hot vents, and very salty places like the Dead Sea.

Characteristics of the four phyla of archaea are described.

26
Both bacteria and archaea that are adapted to grow under extreme conditions are called extremophiles,
meaning “lovers of extremes.” Extremophiles have been found in all kinds of places: the depth of the
oceans, hot springs, the Artic and the Antarctic, in very dry places, deep inside Earth, in harsh chemical
environments, and in high-radiation environments, just to mention a few.

There are a number of groups of extremophiles, defined by their preferred (or at least, survivable)
conditions. Of course, habitats can be extreme in multiple ways. For example, a soda lake is both salty
and alkaline, so organisms that live in it must be both halophiles (salt-loving) and alkaliphiles (high pH-
loving).

The table below lists classes of extremophiles and the conditions they prefer:

Extremophile type Typical conditions for growth

Acidophiles pH 3 or below
Alkaliphiles pH 9 or above
Thermophiles Temperature 60 - 80°C (140 - 176°F)
Hyperthermophiles Temperature 80 - 122°C (176 - 250°F)
Psychrophiles Temperature of -15 - 10°C (5 - 50°F) or lower
Halophiles Salt concentration of at least 0.2M
Osmophiles High sugar concentration

The many "mystery prokaryotes"

For many years, the main approach to studying prokaryotes was to grow them in the lab. If an organism
could be grown on an agar plate or in a liquid culture, then it could be studied, analyzed, and added to
our growing catalog of prokaryotic species and strains.

Some prokaryotes, however, can't grow in a laboratory setting (at least, not under the conditions
scientists have tried). In fact, an estimated 99% of bacteria and archaea are unculturable!

Two bacterial plates with red agar are shown. Both plates are covered with bacterial colonies. On the
right plate, which contains hemolytic bacteria, the red agar has turned clear where bacteria are growing.
On the left plate, which contains non-hemolytic bacteria, the agar is not clear.

27
This represents a pretty huge gap in our understanding of what prokaryotes are out there. For context,
there are 8.7 million known eukaryotic species. If the culturability problem applied to eukaryotes in the
same degree as prokaryotes, we would only know of 87,000 of these species. This would make for a very
empty tree of life, and a very incomplete understanding of what eukaryotes (as a group) are like. For
instance, we might know that there were animals, but be in the dark about plants or fungi!

What is a prokaryotic species?

In order to talk about finding prokaryotic species, we probably need to define what they are. This may
seem like a basic question, but it's a complex and even controversial one if you're a microbiologist.

For eukaryotes, most scientists define a species as a group of organisms that can interbreed and have
fertile offspring. This definition makes sense for species that reproduce sexually, but it doesn't work so
well for organisms like bacteria. Bacteria reproduce asexually to make clones of themselves—they don't
interbreed.

Scientists instead classify bacteria and archaea into taxonomic groups based on similarities in appearance,
physiology, and genes. Many are given names using traditional Linnean taxonomy, with a genus and
species. Still, the question of how and whether prokaryotes should be grouped into species remains a
topic of debate among scientists. The right “species concept” for these organisms is still a work in
progress.

Metagenomics: A new window on microbes

Scientists estimate there may be millions of prokaryotic species (or species-like groups), but we know very
little about most of them. This is starting to change thanks to large-scale DNA sequencing.

DNA sequencing makes it possible for scientists to study entire prokaryotic communities in their natural
habitats – including the many prokaryotes that are unculturable, and would previously have been
"invisible" to researchers.

The collective genome of such a community is called its metagenome, and the analysis of metagenome
sequences is known as metagenomics. Prokaryotic metagenomics is one of the areas of biology that I find
coolest and most mysterious.

For example, a DNA sample can be taken from a hot spring microbial mat, such as the beautiful,
multicolored mats found in Yellowstone National Park. Even a tiny sample from this rich community
includes many, many individuals of different species.

By sequencing and analyzing metagenome DNA samples, scientists can sometimes piece together entire
genomes of previously unknown species. In other cases, they use sequence information from specific
genes to figure out what types of prokaryotes are present (and how they are related to each other or to
known species). The genes found in the DNA samples can also provide clues about the metabolic
strategies of the organisms in the community.

28
 PART II: Viruses

Viruses

Watch “Viruses”

Read: “Intro to viruses”

Key points:
• A virus is an infectious particle that reproduces by "commandeering" a host cell and using its machinery to
make more viruses.
•
• A virus is made up of a DNA or RNA genome inside a protein shell called a capsid. Some viruses have an
internal or external membrane envelope.
•
• Viruses are very diverse. They come in different shapes and structures, have different kinds of genomes,
and infect different hosts.
•
• Viruses reproduce by infecting their host cells and reprogramming them to become virus-making
"factories."

Introduction
Scientists estimate that there are roughly 1031 viruses at any given moment. That’s a one with 31 zeroes
after it! If you were somehow able to wrangle up all 1031 of these viruses and line them end-to-end, your
virus column would extend nearly 200 light years into space. To put it another way, there are over ten
million times more viruses on Earth than there are stars in the entire universe.

Does that mean there are 1031 viruses just waiting to infect us? Actually, most of these viruses are found
in oceans, where they attack bacteria and other microbes. It may seem odd that bacteria can get a virus,
but scientists think that every kind of living organism is probably host to at least one virus!

What is a virus?
A virus is an tiny, infectious particle that can reproduce only by infecting a host cell. Viruses
"commandeer" the host cell and use its resources to make more viruses, basically reprogramming it to
become a virus factory. Because they can't reproduce by themselves (without a host), viruses are not
considered living. Nor do viruses have cells: they're very small, much smaller than the cells of living
things, and are basically just packages of nucleic acid and protein.

Still, viruses have some important features in common with cell-based life. For instance, they have
nucleic acid genomes based on the same genetic code that's used in your cells (and the cells of all living
creatures). Also, like cell-based life, viruses have genetic variation and can evolve. So, even though they
don't meet the definition of life, viruses seem to be in a "questionable" zone. (Maybe viruses are
actually undead, like zombies or vampires!)

How are viruses different from bacteria?

Even though they can both make us sick, bacteria and viruses are very different at the biological level.
Bacteria are small and single-celled, but they are living organisms that do not depend on a host cell to
reproduce. Because of these differences, bacterial and viral infections are treated very differently. For
instance, antibiotics are only helpful against bacteria, not viruses.

Bacteria are also much bigger than viruses. The diameter of a typical virus is about 20-300 nanometers
(nm = 10-9m). This is considerably smaller than a typical E. coli bacterium, which has a diameter of
roughly 1000 nm! Tens of millions of viruses could fit on the head of a pin.

29
 The structure of a virus
There are a lot of different viruses in the world. So, viruses vary a ton in their sizes, shapes, and life
cycles. If you're curious just how much, I recommend playing around with the ViralZone website. Click on
a few virus names at random, and see what bizarre shapes and features you find!

Viruses do, however, have a few key features in common. These include:
•
• A protective protein shell, or capsid
•
• A nucleic acid genome made of DNA or RNA, tucked inside of the capsid
•
• A layer of membrane called the envelope (some but not all viruses)

Let's take a closer look at these features.

Diagram of a virus. The exterior layer is a membrane envelope. Inside the envelope is a protein capsid,
which contains the nucleic acid genome.

Virus capsids
The capsid, or protein shell, of a virus is made up of many protein molecules (not just one big, hollow
one). The proteins join to make units called capsomers, which together make up the capsid. Capsid
proteins are always encoded by the virus genome, meaning that it’s the virus (not the host cell) that
provides instructions for making them.

Capsids come in many forms, but they often take one of the following shapes (or a variation of these
shapes):

1. Icosahedral – Icosahedral capsids have twenty faces, and are named after the twenty-sided shape called
an icosahedron.
2.
3. Filamentous – Filamentous capsids are named after their linear, thin, thread-like appearance. They may
also be called rod-shaped or helical.
4.
5. Head-tail –These capsids are kind of a hybrid between the filamentous and icosahedral shapes. They
basically consist of an icosahedral head attached to a filamentous tail.

30
 Diagram of icosahedral (roughly spherical), filamentous (rod-like), and head-tail (icosahedral head
attached to filamentous tail) virus capsid shapes.

Virus envelopes
In addition to the capsid, some viruses also have a lipid membrane known as an envelope. Virus envelopes
can be external, surrounding the entire capsid, or internal, found beneath the capsid.

Viruses with envelopes do not provide instructions for the envelope lipids. Instead, they "borrow" a patch
from the host membranes on their way out of the cell. Envelopes do, however, contain proteins that are
specified by the virus, which often help viral particles bind to host cells.

Diagram of enveloped icosahedral virus.

Although envelopes are common, especially among animal viruses, they are not found in every virus (i.e.,
are not a universal virus feature).

Virus genomes
All viruses have genetic material (a genome) made of nucleic acid. You, like all other cell-based life, use
DNA as your genetic material. Viruses, on the other hand, may use either RNA or DNA, both of which are
types of nucleic acid.

We often think of DNA as double-stranded and RNA as single-stranded, since that's typically the case in
our own cells. However, viruses can have all possible combos of strandedness and nucleic acid type
(double-stranded DNA, double-stranded RNA, single-stranded DNA, or single-stranded RNA). Viral genomes
also come in various shapes, sizes, and varieties, though they are generally much smaller than the
genomes of cellular organisms.

31
 Notably, DNA and RNA viruses always use the same genetic code as living cells. If they didn't, they would
have no way to reprogram their host cells!

What is a viral infection?

In everyday life, we tend to think of a viral infection as the nasty collection of symptoms we get when
catch a virus, such as the flu or the chicken pox. But what's actually happening in your body when you
have a virus?

At the microscopic scale, a viral infection means that many viruses are using your cells to make more
copies of themselves. The viral lifecycle is the set of steps in which a virus recognizes and enters a host
cell, "reprograms" the host by providing instructions in the form of viral DNA or RNA, and uses the host's
resources to make more virus particles (the output of the viral "program").

For a typical virus, the lifecycle can be divided into five broad steps (though the details of these steps will
be different for each virus):

Steps of a viral infection, illustrated generically for a virus with a + sense RNA genome.
1. Attachment. Virus binds to receptor on cell surface.
2. Entry. Virus enters cell by endocytosis. In the cytoplasm, the capsid comes apart, releasing the RNA
genome.
3. Replication and gene expression. The RNA genome is copied (this would be done by a viral enzyme, not
shown) and translated into viral proteins using a host ribosome. The viral proteins produced include
capsid proteins.
4. Assembly. Capsid proteins and RNA genomes come together to make new viral particles.
5. Release. The cell lyses (bursts), releasing the viral particles, which can then infect other host cells.

1. Attachment. The virus recognizes and binds to a host cell via a receptor molecule on the cell surface.
32
 Virus binding to its receptor on the cell surface.
2.
3. Entry. The virus or its genetic material enters the cell.

Routes of entry include endocytosis (in which the membrane folds inward to bring the virus into the cell
in a bubble) and direct fusion of the viral particle with the membrane, releasing its contents into the
cell.

4. Genome replication and gene expression. The viral genome is copied and its genes are expressed to
make viral proteins.

The viral genome is copied, and its genes are also expressed to make viral proteins.

5. Assembly. New viral particles are assembled from the genome copies and viral proteins.

Proteins of the capsid assemble around the viral genome, forming a new viral particle with the genome
on the inside (encased by the capsid).
6.
7. Release. Completed viral particles exit the cell and can infect other cells.
33
 Viruses may exit through lysis of the cell, exocytosis, or budding at the plasma membrane.

The diagram above shows how these steps might occur for a virus with a single-stranded RNA genome. You
can see real examples of viral lifecycles in the articles on bacteriophages (bacteria-infecting viruses)
and animal viruses.

Read: “Bacteriophages”

Introduction
Even bacteria can get a virus! The viruses that infect bacteria are called bacteriophages, and certain
bacteriophages have been studied in detail in the lab (making them some of the viruses we understand
best).

In this articles, we'll take a look at two different cycles that bacteriophages may use to infect their
bacterial hosts:

• The lytic cycle: The phage infects a bacterium, hijacks the bacterium to make lots of phages, and then
kills the cell by making it explode (lyse).
•
• The lysogenic cycle: The phage infects a bacterium and inserts its DNA into the bacterial chromosome,
allowing the phage DNA (now called a prophage) to be copied and passed on along with the cell's own
DNA.

Let's take a closer look at each of these cycles.

A bacteriophage is a virus that infects bacteria

A bacteriophage, or phage for short, is a virus that infects bacteria. Like other types of viruses,
bacteriophages vary a lot in their shape and genetic material.

• Phage genomes can consist of either DNA or RNA, and can contain as few as four genes or as many as
several hundred.
•
• The capsid of a bacteriophage can be icosahedral, filamentous, or head-tail in shape. The head-tail
structure seems to be unique to phages and their close relatives (and is not found in eukaryotic viruses).

34
 Icosahedral phage, head-tail phage, and filamentous phage.

Bacteriophage infections
Bacteriophages, just like other viruses, must infect a host cell in order to reproduce. The steps that make
up the infection process are collectively called the lifecycle of the phage.

Some phages can only reproduce via a lytic lifecycle, in which they burst and kill their host cells. Other
phages can alternate between a lytic lifecycle and a lysogenic lifecycle, in which they don't kill the host
cell (and are instead copied along with the host DNA each time the cell divides).

Let's take closer look at these two cycles. As an example, we'll use a phage called lambda (λ), which
infects E. coli bacteria and can switch between the lytic and lysogenic cycles.

Lytic cycle
In the lytic cycle, a phage acts like a typical virus: it hijacks its host cell and uses the cell's resources to
make lots of new phages, causing the cell to lyse (burst) and die in the process.

35
 1. Attachment: Proteins in the "tail" of the phage bind to a specific receptor (in this case, a sugar
transporter) on the surface of the bacterial cell.
2. Entry: The phage injects its double-stranded DNA genome into the cytoplasm of the bacterium.
3. DNA copying and protein synthesis: Phage DNA is copied, and phage genes are expressed to make
proteins, such as capsid proteins.
4. Assembly of new phage: Capsids assemble from the capsid proteins and are stuffed with DNA to make
lots of new phage particles.
5. Lysis: Late in the lytic cycle, the phage expresses genes for proteins that poke holes in the plasma
membrane and cell wall. The holes let water flow in, making the cell expand and burst like an overfilled
water balloon.
Cell bursting, or lysis, releases hundreds of new phages, which can find and infect other host cells
nearby.

The stages of the lytic cycle are:

1. Attachment: Proteins in the "tail" of the phage bind to a specific receptor (in this case, a sugar
transporter) on the surface of the bacterial cell.
2.
3. Entry: The phage injects its double-stranded DNA genome into the cytoplasm of the bacterium.
4.
5. DNA copying and protein synthesis: Phage DNA is copied, and phage genes are expressed to make
proteins, such as capsid proteins.
6.
7. Assembly of new phage: Capsids assemble from the capsid proteins and are stuffed with DNA to make
lots of new phage particles.
8.

36
9. Lysis: Late in the lytic cycle, the phage expresses genes for proteins that poke holes in the plasma
membrane and cell wall. The holes let water flow in, making the cell expand and burst like an overfilled
water balloon.

Cell bursting, or lysis, releases hundreds of new phages, which can find and infect other host cells nearby.
In this way, a few cycles of lytic infection can let the phage spread like wildfire through a bacterial
population.

Lysogenic cycle
The lysogenic cycle allows a phage to reproduce without killing its host. Some phages can only use the
lytic cycle, but the phage we are following, lambda (λ), can switch between the two cycles.

In the lysogenic cycle, the first two steps (attachment and DNA injection) occur just as they do for the
lytic cycle. However, once the phage DNA is inside the cell, it is not immediately copied or expressed to
make proteins. Instead, it recombines with a particular region of the bacterial chromosome. This causes
the phage DNA to be integrated into the chromosome.

Lysogenic cycle:
1. Attachment. Bacteriophage attaches to bacterial cell.
2. Entry. Bacteriophage injects DNA into bacterial cell.
3. Integration. Phage DNA recombines with bacterial chromosome and becomes integrated into the
chromosome as a prophage.
4. Cell division. Each time a cell containing a prophage divides, its daughter cells inherit the prophage.
37
 The integrated phage DNA, called a prophage, is not active: its genes aren't expressed, and it doesn't
drive production of new phages. However, each time a host cell divides, the prophage is copied along
with the host DNA, getting a free ride. The lysogenic cycle is less flashy (and less gory) than the lytic
cycle, but at the end of the day, it's just another way for the phage to reproduce.

Under the right conditions, the prophage can become active and come back out of the bacterial
chromosome, triggering the remaining steps of the lytic cycle (DNA copying and protein synthesis, phage
assembly, and lysis).

1. Prophage exits chromosome and becomes its own circularized DNA molecule.
2. Lytic cycle commences.

To lyse or not to lyse?

How does a phage "decide" whether to enter the lytic or lysogenic cycle when it infects a bacterium? One
important factor is the number of phages infecting the cell at once. Larger numbers of co-infecting
phages make it more likely that the infection will use the lysogenic cycle. This strategy may help prevent
the phages from wiping out their bacterial hosts (by toning down the attack if the phage-to-host ratio gets
too high).

What triggers a prophage to pop back out of the chromosome and enter the lytic cycle? At least in the
laboratory, DNA-damaging agents (like UV radiation and chemicals) will trigger most prophages in a
population to re-activate. However, a small fraction of the prophages in a population spontaneously "go
lytic" even without these external cues.

Bacteriophage vs. antibiotics

Before antibiotics were discovered, there was considerable research on bacteriophages as a treatment for
human bacterial diseases. Bacteriophages attack only their host bacteria, not human cells, so they are
potentially good candidates to treat bacterial diseases in humans.

After antibiotics were discovered, the phage approach was largely abandoned in many parts of the world
(particularly English-speaking countries). However, phages continued to be used for medical purposes in a
number of countries, including Russia, Georgia, and Poland, where they remain in use today.

There is increasing interest in bringing back the "phage approach" elsewhere, as antibiotic-resistant
bacteria become more and more of a problem. Research is still needed to see how safe and effective
phages are, but who knows? One day, your doctor might write you a prescription for phages instead of
penicillin!

Read: “Animal & human viruses”

Key points:
• There are many different kinds of viruses that infect humans and other animals, some causing serious
illness and others not.
•
• Viruses can be classified according to the Baltimore system, and human-infecting viruses fall into all of
its seven categories.
•
38
• The human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS),
is a retrovirus.
•
Introduction
Have you ever had the flu or the chicken pox? If so, then you've had a close encounter of the viral kind!
Whether you dream of one day finding a cure for AIDS or simply hope to avoid this year's flu bug, you're
probably familiar with the suffering that can be caused by viral infections (and minimized by vaccines and
treatments).

Human viruses come in many types and have a wide range of effects. Some make us sick for a day or two
before going away, while others are lifelong. Some are a minor annoyance, while others, such as Ebola,
can cause life-threatening complications.

Because of their impact on our health and quality of life, many human viruses (and related animal viruses)
have been studied in detail. Let's take a look at some of these viruses.

What does an animal virus look like?

Like other viruses, animal viruses are tiny packages of protein and nucleic acid. They have a protein shell,
or capsid, and genetic material made of DNA or RNA that's tucked inside the caspid. They may also
feature an envelope, a sphere of membrane made of lipid.

Animal virus capsids come in many shapes. One of the craziest-looking (to me, at least) is the Ebola virus,
which has a long, thread-like structure that loops back on itself. A more "standard-looking" virus,
chikungunya, is shown below for comparison: chikungunya looks like a sphere, but is actually a 20-sided
icosahedron.

Animal virus genomes consist of either RNA or DNA, which may be single-stranded or double-stranded.
Animal viruses may use a range of strategies (including some surprising and bizarre ones) to copy and use
their genetic material, as we'll see in sections below.

How do animal viruses infect cells?

Animal viruses, like other viruses, depend on host cells to complete their life cycle. In order to reproduce,
a virus must infect a host cell and reprogram it to make more virus particles.

The first key step in infection is recognition: an animal virus has special surface molecules that let it bind
to receptors on the host cell membrane. Once attached to a host cell, animal viruses may enter in a
variety of ways: by endocytosis, where the membrane folds in; by making channels in the host membrane
(through which DNA or RNA can be injected); or, for enveloped viruses, by fusing with the membrane and
releasing the capsid inside of the cell.
39
After the virus uses the host cell's resources to make new viral proteins and genetic material, viral
particles assemble and prepare to exit the cell. Enveloped animal viruses may bud from the cell
membrane as they form, taking a piece of the plasma membrane or internal membranes in the process. In
contrast, non-enveloped virus particles, such as rhinoviruses, typically build up in infected cells until the
cell bursts and/or dies and the particles are released.

Consequences of an infection
Viruses are associated with a variety of human diseases. The diagram below shows some common
examples of viral infections that affect different systems of the human body:

The illustration shows an overview of human viral diseases.

Some viral infections follow the classic pattern of acute disease: symptoms worsen for a short period, but
in most cases, the virus is cleared from the body by the immune system and the patient recovers.
Examples include the common cold and influenza.

Other viruses, such as the hepatitis C virus, cause long-term chronic infections. Still other viruses, such
as human herpesviruses 6 and 7, which in some cases cause the minor childhood disease roseola, may
form productive infections (ones where new viral particles are produced) without causing any symptoms
at all in the host. In these cases, patients are said to have an asymptomatic infection.

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 Classifying animal viruses
Animal viruses come in many types, and they enter, commandeer, and exit cells in a variety of different
ways. How can we organize this mess of viruses in a way that's consistent and makes sense?

The Baltimore system groups viruses according to their type of genetic material and how it's used to
make messenger RNAs (mRNAs), key intermediates in the production of viral proteins and the assembly of
new viruses. A virus's Baltimore group depends on:

• The molecule it uses as genetic material (DNA or RNA)

•
• Whether the genetic material is single- or double-stranded
•
• The steps the virus uses to make an mRNA

The Baltimore system divides viruses into seven groups. You can see the basic features of each group,
including its genetic material and the pathway it uses to make an mRNA, in the diagram below:

•
Human viruses are found in all seven Baltimore groups, while plant and bacterial viruses are found only in
a subset of groups. If we want to develop a drug to target a virus, it's important for us to know the details
of its life cycle—including its Baltimore group and other aspects of its biology—in order to block that cycle
effectively.

The retrovirus HIV-1

Retroviruses, found in Baltimore group VI, have a unique and fascinating life cycle. They are of special
importance because human immunodeficiency virus(HIV), the virus that causes acquired immune
deficiency syndrome, or AIDS, is a retrovirus.

A retrovirus genome is single-stranded RNA and comes in two copies per viral particle. The RNA must be
converted into double-stranded DNA by an enzyme called reverse transcriptase, reversing the normal
flow of information from DNA to RNA to protein in cells.

The double-stranded DNA enters the nucleus of the host cell and is inserted into the host genome by an
enzyme called integrase. mRNA can then be made by transcription of the viral DNA, which, as a

41
 permanent part of the host cell's genome, is called a provirus. The mRNA is read to produce viral proteins
and may also serve as a genome for new viral particles that assemble and bud from the cell.

The diagram below shows the key life cycle stages of the HIV-1 virus, the strain responsible for most cases
of HIV infection.

Anti-HIV drugs inhibit viral replication at many different phases of the HIV cycle. These drugs include:

• Fusion inhibitors, which block fusion of the HIV viral envelope with the plasma membrane of the host cell
•
• Reverse transcriptase inhibitors, which impair the conversion of the RNA genome into double-stranded
DNA
•
• Integrase inhibitors, which inhibit the integration of the viral DNA into the host genome
42
•
• Protease inhibitors, which block processing of viral proteins

"Cocktails" containing multiple drugs are usually most effective at slowing the progression of the infection
and keeping viral levels low. You can learn why this is the case in the virus evolution article.
For more on symptoms, treatment, and prevention of HIV and AIDS, please see the Health & Medicine
section on HIV and AIDS.

Read: “Evolution of viruses”

Key points:
• Viruses undergo evolution and natural selection, just like cell-based life, and most of them evolve rapidly.
•
• When two viruses infect a cell at the same time, they may swap genetic material to make new, "mixed"
viruses with unique properties. For example, flu strains can arise this way.
•
• RNA viruses have high mutation rates that allow especially fast evolution. An example is the evolution of
drug resistance in HIV.
•
Introduction
Have you ever wondered why a different strain of flu virus comes around every year? Or how HIV, the
virus that causes AIDS, can become drug-resistant?

The short answer to these questions is that viruses evolve. That is, the "gene pool" of a virus population
can change over time. In some cases, the viruses in a population—such as all the flu viruses in a
geographical region, or all the different HIV particles in a patient's body—may evolve by natural
selection. Heritable traits that help a virus reproduce (such as high infectivity for influenza, or drug
resistance for HIV) will tend to get more and more common in the virus population over time.

What is evolution?
Evolution is a change in the gene pool and/or heritable traits of a population over time

Natural selection is a mechanism of evolution in which heritable traits that help organisms survive and
reproduce (in the current environment) become more and more common in the population over time.
Natural selection can allow a population to adapt, or become better suited, to its environment.

Viruses undergo evolution (by natural selection and other mechanisms) just as cell-based organisms do.
Visit the evolution topic to learn more about evolution and natural selection.

Not only do viruses evolve, but they also tend to evolve faster than their hosts, such as humans. That
makes virus evolution an important topic—not just for biologists who study viruses, but also for doctors,
nurses, and public health workers, as well as anyone who might be exposed to a virus. (Hint: that means
all of us!)

Variation in viruses
Natural selection can only happen when it has the right starting material: genetic variation. Genetic
variation means there are some genetic (heritable) differences in a population. In viruses, variation
comes from two main sources:

• Recombination: viruses swap chunks of genetic material (DNA or RNA).

•
• Random mutation: a change occurs in the DNA or RNA sequence of a virus.

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We can see variation and evolution of viruses all around us if we know where to look—for instance, in the
new flu strains that appear each year.

Mixing it up: Recombination

Before we looks specifically at the flu, let's examine how viruses swap DNA and RNA in a process
called recombination.

Recombination usually happens when two viruses have infected the same cell at the same time. Since
both viruses are using the cell to crank out more virus particles, there will be lots of virus parts – including
newly made genomes – floating around in the cell at once.

Reassortment between two viral strains that infect the same cell.
Strain A has eight segments of genetic material. Strain B also has eight segments, which bear similar
genes but in different versions.
Both strains co-infect the same host cell. The segments get mixed up in the host cell.
This results in the production of a reassortant virus. The reassortant virus has segments 3, 6, 7, and 8
from strain A and segments 1, 2, 4, and 5 from strain B.

Under these circumstances, recombination can happen in two different ways. First, similar regions of viral
genomes can pair up and exchange pieces, physically breaking and re-connecting the DNA or RNA. Second,
viruses with different segments (kind of like tiny chromosomes) can swap some of those segments, a
process called reassortment.

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Recombination and influenza ("the flu")
Influenza ("flu") viruses are masters of reassortment. They have eight RNA segments, each carrying one or
a few genes.

When two influenza viruses infect the same cell at the same time, some of the new viruses made inside of
the cell may have a mix of segments (e.g., segments 1-4 from strain A and segments 5-8 from strain B).

Human influenza virus and bird influenza virus infect same pig cell. Each has eight segments of RNA in its
genome.
The segments get mixed up as new viruses are made in the cell.
Various different combinations could be made. For example, we could get one virus particle with
segments 1-4 from the human virus and segments 5-8 from the other, and vice versa.

45
Pigs in particular are well-known "mixing vessels" for influenza viruses. Pig cells can be recognized, and
thus infected, by both human and bird influenza viruses (as well as pig viruses. If a cell in the pig is
infected with two types of virus at the same time, it may release new viruses that contain a mixture of
genetic material from the human and bird viruses.

This kind of swap is common for influenza viruses in nature. For example, remember the H1N1 influenza
strain ("swine flu") that caused a pandemic in 2009? H1N1 had RNA segment from human and bird viruses,
as well as pig viruses from both North America and Asia. This combo reflects a series of reassortments
that occurred step by step over many years to produce this H1N1 strain.

Viral mutations
We've seen how recombination can affect virus evolution, but what about mutation? A mutation is a
permanent change in the genetic material (DNA or RNA) of a virus. A mutation can happen if there is a
mistake during copying of the DNA or RNA of the virus.

Some viruses have very high mutation rates, but this is not universally the case. In general, RNA viruses
tend to have high mutation rates, while DNA viruses tend to have low mutation rates.

Why is this the case? The key difference lies in the copying machinery. Most DNA viruses copy their
genetic material using enzymes from the host cell, called DNA polymerases, which “proofread" (catch and
fix mistakes as they go). RNA viruses instead use enzymes called RNA polymerases, which don't proofread
and thus make many more mistakes.

Case study: HIV drug resistance

Human immunodeficiency virus (HIV) is the virus that causes acquired immune deficiency
syndrome (AIDS). HIV is an RNA virus with a high mutation rate and evolves rapidly, leading to the
emergence of drug-resistant strains.

HIV's high mutation rate

Because RNA viruses like HIV have a high mutation rate, there will be lots of genetic variation in the
population of HIV viruses in a patient's body. Many of the mutations will be harmful, and the mutant
viruses will simply "die" (fail to reproduce). However, some mutations help viruses reproduce under
specific conditions. For instance, a mutation may provide resistance to a drug.

Evolution of drug resistance in HIV

Certain drugs can block the replication of HIV by inhibiting key viral enzymes. Taking one of these drugs
will at first reduce a patient's viral levels. After awhile, however, the HIV viruses typically "bounce back"
and return to high levels, even though the drug is still present. In other words, a drug-resistant form of
the virus emerges.

To see why this took place, let's use the example of a specific type of antiviral drug, a reverse
transcriptase inhibitor. Reverse transcriptase inhibitors, like the nevirapine molecule shown in the
diagram below, bind to a viral enzyme called reverse transcriptase (the red-and-brown structure). The
drug keeps the enzyme from doing its job of copying the RNA genome of HIV into DNA. If this enzyme is
inactive, an HIV virus can't permanently infect a cell.

46
 Ball-and-stick molecular model of HIV reverse transcriptase enzyme with the reverse transcriptase
molecule nevirapine bound to it.

Most HIV viruses are stopped by nevirapine. However, a very small fraction of the viruses in the HIV
population will (by random chance) have a mutation in the gene for reverse transcriptase that makes
them resistant to the drug. For instance, they might have a genetic change that alters the drug's binding
site on the enzyme, so that the drug is no longer able to latch on and inhibit enzyme activity.

The viruses with this resistance mutation will reproduce despite the presence of the drug and, over
generations, can re-establish the viral levels present before the drug was administered. Not only that, but
the entire virus population will now be resistant to the drug!

HAART drug resistance

If HIV can evolve its way around a drug, how can the virus be stopped? What seems to work best is a
combination approach, with three or more drugs taken at the same time. This approach to treatment is
called highly active antiretroviral therapy, or HAART for short. The drugs given in a HAART "cocktail"
typically target different parts of the HIV lifecycle.

The HAART approach works because it's relatively unlikely that any one HIV virus in a population will
happen to have three mutations that give resistance to all three drugs at the same time. Although multi-
drug-resistant forms of the virus do eventually evolve, multi-drug combinations considerably slow the
evolution of resistance.

To learn more about the biology of HIV, please see the article on virus lifecycles. To learn more about
symptoms, treatment, and prevention of HIV and AIDS, please see the Health & Medicine section on HIV
and AIDS.

Why do viruses evolve so fast?

Viruses evolve faster than humans. Why is this the case?

As we saw in the case of HIV, some viruses have a high mutation rate, which helps them evolve quickly by
providing more variation as starting material. Two other factors that contribute to the fast evolution of
viruses are large population size and rapid lifecycle.

The bigger the population, the higher the odds that it'll have a virus with a particular random mutation
(e.g., one for drug resistance or high infectivity) on which natural selection can act. Also, viruses
reproduce quickly, so their populations evolve on shorter timescales than those of their hosts. For

47
instance, the HIV virus goes through its lifecycle in just 52 hours, as compared to roughly 20 years for the
human lifecycle!

What tools do we have to combat fast-evolving viruses? Taking steps to prevent transmission, identifying
new drugs for treatment, and developing and using vaccines are all important strategies.

Read: “The biology of Zika virus”

Introduction
You may have heard about Zika virus in the news. Because of Zika’s recent spread in the Americas, many
people want to understand more about this virus.

In this article, we’ll take a look at Zika from a biological standpoint. First, we’ll examine the structure,
life cycle, and transmission mode of Zika virus, seeing how it infects cells. Then, we’ll look at the effects
of Zika on humans, as well as the prospects for controlling and managing the virus.

What is Zika virus?

Zika belongs to a group of viruses called the flaviviruses, which includes dengue, West Nile, and yellow
fever. Flaviviruses are tiny structures made up of protein, RNA (a molecule related to DNA), and a lipid
membrane. Each viral particle consists of a single-stranded RNA genome tucked inside a protein shell
called a capsid, surrounded by an external sphere of membrane known as the envelope. You can see Zika
virus particles in the microcope image below right, where they appear as small, dark spheres. One
particle is marked with an arrow.

Left, schematic of a Zika virus particle in cross-section and from an exterior view. The virus consists of
an RNA molecule, a surrounding protein capsid, and a membrane envelope around the capsid. The
envelope contains many proteins that cover the majority of the virus particle's surface.
Right, transmission electron micrograph of Zika virus particles. The particles are visible as small spheres
with a dark core and a lighter rim.

A defining characteristic of viruses is that they cannot reproduce on their own. Instead, they must infect
host cells and “reprogram” them to become virus-producing factories. Zika virus is no exception. It cannot
replicate by itself, but can infect and replicate inside of the cells of several species, including humans,
monkeys, and mosquitoes. Although we don't know which cell types Zika targets in the human body,
studies with cultured cells (cells grown in a dish) show that Zika can infect a variety of immune cells
found in human skin.

Where did Zika come from?

Zika is not a new virus. It was first isolated from a monkey in the Zika forest of Uganda in 1947, and the
first human case was reported in 1954. A few additional cases were reported in Africa in the following
years, and, starting at the end of the 1960s, in equatorial Asia as well. No serious health complications or
outbreaks were documented during this period, and blood tests for antibodies against Zika suggested that

48
people in the affected areas were widely exposed to the virus. For these reasons, Zika was classified as a
benign, sporadically occurring virus.

In 2007, the first documented outbreak of Zika took place, on Yap Island in Micronesia. In this outbreak, it
was estimated that over 70% of the island's population above the age of 3 was infected with the virus.
Although no serious complications or hospitalizations were reported, an outbreak on this scale was
unprecedented, as the total number of reported Zika cases to that point had been less than 15. A lack of
previous exposure to Zika may have made the population of Yap Island more susceptible to outbreak than
populations in the virus's normal range.

In 2013 and 2014, another Zika outbreak occurred, in French Polynesia and the surrounding islands. During
this outbreak, health authorities noticed an increased frequency of neurological disorders, including
Guillain-Barré syndrome (which causes temporary paralysis), as well as nervous system and brain
abnormalities in infants.

The first locally acquired cases of Zika in the Americas were reported in Brazil in May of 2015. Since then,
the presence of Zika has been reported in many countries throughout South and Central America. The
strains of Zika virus currently found in the Americas are closely related to those from the French Polynesia
outbreak, suggesting that the virus may have reached Brazil from French Polynesia.

How is Zika transmitted?

The primary mode of Zika transmission is through mosquitoes in the genus Aedes. In this regard, Zika is
similar to related flaviviruses such as dengue, yellow fever, and West Nile virus. When a mosquito eats a
blood meal from a person infected with Zika, the virus can infect the cells of the mosquito. After the
mosquito’s infection has developed (usually after a period of about a week and a half), its saliva will
contain viral particles. When it bites another human to obtain a blood meal, the viral particles can be
transmitted to the human, who may contract Zika.

Photograph of Aedes albopictusmosquito.

Although this transmission pathway is by far the most common for Zika virus, other modes of transmission
are also possible. For instance, a pregnant woman who contracts Zika may transmit the virus to her
growing fetus, or to the baby during birth. There have also been a few documented cases of Zika
transmission through sexual contact or through blood transfusions from a Zika-infected donor.

How does Zika infect cells?

Once Zika virus particles are in the human body, they must enter individual cells in order to replicate and
make more viruses. Cell entry is possible because a Zika virus particle carries specific proteins on its outer
envelope that interact with receptor proteins on human cells. When the viral proteins bind to cell
receptors, they “trick” the cells into taking up the viral particle.

49
Inside the cell, the RNA genome of the virus is released into the cytoplasm, or fluid-filled main
compartment, of the cell. There, the RNA molecule is “read” (translated) by enzymes in the cell to make
a long protein, which is chopped up into a number of smaller proteins (see image at left). Some of these
proteins are the structural components needed to make new viral particles, such as capsid and envelope
proteins. Other viral proteins copy and process the RNA genome.

Viral proteins and copies of the RNA genome assemble at the surface of the endoplasmic reticulum (ER), a
membrane compartment that’s part of the cell’s export system. New viral particles bud off into the
interior of the ER, taking a small patch of ER membrane along with them. This "stolen" membrane will
form the viral envelope. The particles then travel through another structure, the Golgi apparatus, where
they undergo more processing before release at the cell surface. Released viral particles can infect other
cells, continuing the infection cycle.

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What are the symptoms and effects of Zika?
In most cases, the symptoms of Zika infection are very mild. According to the CDC, only 1 in 5 people
infected with Zika will get sick at all, and typical symptoms may include rash, fever, conjunctivitis
(irritation of the eyes), and joint pain. These symptoms generally resolve, and most people do not
experience any lasting effects from Zika.

Pregnant women and their unborn fetuses are at higher risk for harmful effects from Zika. Specifically,
there is a link between Zika infection during pregnancy and a condition called microcephaly (small head)
in newborns. Microcephaly may involve neurological problems or developmental delays, but these effects
vary greatly from person to person. Health authorities are encouraging women who are (or might become)
pregnant to take steps to avoid Zika exposure.

In a very small fraction of cases, Zika may be linked with neurological problems, such as Guillain-Barré
syndrome. Guillain-Barré syndrome is an autoimmune condition that causes paralysis, which is usually
temporary (lasting for weeks or a few months in most cases). An increased frequency of Guillain-Barré
syndrome has been reported in areas with active Zika infections, but researchers are still investigating
whether there is a causal connection.

What can be done about Zika?

In the short term, health authorities have recommended that people protect themselves from Zika by
avoiding exposure to mosquitos in areas where the virus is active. For people in high-risk groups, such as
pregnant women, this might mean postponing travel to areas known to harbor Zika virus. For others who
live in areas where Zika is active, avoiding exposure might mean remaining indoors, using mosquito
repellents and mosquito nets, and removing sources of standing water (which provide a breeding ground
for mosquitoes).

In the longer term, a vaccine against Zika could provide more durable protection. Encouragingly, a
vaccine against dengue, a flavivirus related to Zika, was recently approved for use in Brazil. This vaccine
was built off an inactive version of yellow fever, another related flavivirus, and it’s possible that a similar
strategy could be used for a Zika vaccine. Recently, promising initial results in mice were reported for one
Zika vaccine candidate. However, many more tests will be needed to establish whether this and other
potential vaccines are safe and effective in humans.

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