VIRUSES

There are three main properties distinguishing viruses from other micro organisms:
• Small size: viruses are smaller than other organisms, although they vary
considerably in size, from 10nm to 300nm (we do not need to know exact
values) In contrast, Erythrocytes (that’s red blood cells) are 7500nm in
diameter and Bacteria are 1000nm in diameter.
• Genome: the genome of viruses may be either DNA or RNA; viruses only
contain only one kind of genome (while humans have both DNA and RNA).
• Metabolically inert: viruses have no metabolic activity; they do not possess
active ribosomes or protein-synthesizing apparatus, although some contain
enzymes within them (HIV contains 3 enzymes in its envelope)

Viruses can multiply only inside living cells. Inside these susceptible cells, the virus
redirects the cell’s synthesizing machinery to the manufacture of new virus
components (it basically uses the cells contents to make more viruses). It does
this by transcription of the virus genome or nucleic acid into virus specific
messenger RNA (mRNA). This viral mRNA (vmRNA) then directs the cell to
the replication of new virus particles, which then form the new viruses.

VIRUS STRUCTURE
Viruses consist basically of a core of nucleic acid – the genome – surrounded by a
protein coat. The protein coat protects the genome from inactivation by adverse
environmental factors (like an extreme of pH or temperature)
The protein coat is antigenic and responsible for stimulating the production of
protective antibodies.

The structures that make up a virus particle are:

• Virion: the intact virus particle
• Capsid: the protein coat
• Capsomeres: the protein structural units of which the capsid is composed
• Nucleic Acid Genome: either DNA or RNA.
• Envelope: the particles of many viruses are surrounded by a lipoprotein
envelope containing viral antigens, but also partly derived from outer
membrane or nuclear membrane of the host cell.

VIRUS CLASSIFICATION (Page 1 of lecture notes)

Viruses are categorized using the difference in host, genome, envelope and
arrangement. All viruses contain a viral genome enclosed in a Capsid protein.
• Viruses’ hosts differ between plants, bacteria and animals.
• Their genome differ too:
 Negative single strand RNA, which is a complementary strand that acts as a
template for viral mRNA for replication.
 Positive single strand RNA acts directly as mRNA in host cells, and directly
codes for proteins.
 Retrovirus acts as a template for DNA.
 • Viruses can be categorized by whether they have a lipid envelope or not.
Viruses, such as Herpes, have a lipid envelope taken from the host after a virus
leaves the cell.
• A viruses arrangement also categorizes a virus:
 The most basic being the icosahedral form, in which the virus is a 3D
polyhedron made of 20 triangular faces.
 The helical arrangement involves the virus’ genome being helically shaped
and covered in a cylindrical protein coat.
 The complex arrangement of viruses is the icosahedral arrangement as a head
with protein legs branching from it, allowing attachment to the host
membrane.

When looked through an electron microscope, a virus’s genome will appear black
while its protein fold appears white around it.

THE EFFECT OF TEMPERATURE AND PH ON VIRUSES.

All Viruses are coated by a protein coat; and it is this protein coat that is most
important in determining the shape of the virus. Any condition that affects proteins
will therefore have a direct effect on viruses. An extreme change in pH ionises the
side chains of monomers in the polypeptide chain and therefore will change the
structure of these monomers. This change in structure will have an overall effect on
the shape of the virus. At extreme temperatures, the viruses will also be inactive.

GENOMICS OF VIRUSES (Page 9 of Lecture notes)

Viruses, such as Hepatitis B, have a genome unlike humans as they can their genome
code for many different proteins. It can do this by using same information from DNA,
but reading it differently.

This is illustrated on page 9 of the lecture notes

The virus uses this ability, to read DNA this way, during replication. During
replication, the DNA goes through transcription to make early mRNA, which makes
early proteins. These proteins are enzymes that are needed to make even more
mRNA. So this mechanism is used by the virus to make its own enzymes, which are
needed for replication to occur, using the same strand of DNA.

VIRAL ENTRY INTO THE CELL (Page 5 of Lecture Notes)

There are many ways in which a virus can enter a cell:
• An un-enveloped virus may simply travel through the lipid bi-layer into the
cytoplasm.
• An unenveloped virus may use its protein sub-units to act as receptors, which
then bind to the plasma membrane receptors. Once attached, the cell
membrane will surround the virus, forming an endosome, which then is
released into the cytoplasm.
• An enveloped virus’ receptors attach onto the plasma membrane receptors and
once attached, the virus’s lipid envelope will integrate itself with the plasma
membrane, releasing the nucleocapsid into the cytoplasm.
• An enveloped virus’ receptors attach onto the plasma membrane receptors and
once attached, the plasma membrane will surround the virus’ lipid envelope,
 forming an endosome, which is then released into the cytoplasm. This
endosome has therefore got a nucleocapsid surrounded by two lipid envelopes.

VIRAL EXIT/RELEASE FROM THE CELL

There are two ways in which a virus can exit a cell:
• Lysis: In which the virus exits the cell membrane, and acquire part the host’s
cell membrane to form its own lipid envelope. Lysis eventually results in the
death of the cell.
• Budding: In which viruses acquire their external envelope as a fragment of the
host cell membrane using essential proteins, usually the hosts proteins. This
method helps the virus leave the cell without lysing the cell, allowing the cell
to produce more viruses.

LIFE CYCLE OF A DOUBLE STRANDED DNA VIRUS (Page 10)

Hepatitis B is a form of double stranded DNA viruses.
The diagram below shows the life cycle of the virus with these 6 steps:
1.) The virus enters the cytoplasm of the virus with its lipid envelope binding to
the cell membrane through fusion and releasing the virus capsid into the
cytoplasm.
2.) The virus travels to the nucleur membrane via a microtubule, and enters into
the nucleus through a nucleur pore.
3.) The DNA strand of the Virus Genome goes through transcription to form
EARLY mRNA. The mRNA is transported out of the nucleus to the cytoplasm
where it goes through translation on ribosomes to form EARLY PROTEINS.
These early proteins are enzymes, and are transported into the nucleus to the
viral DNA.
4.) The early proteins are used as the viral DNA goes through transcription again
to form LATE mRNA. This mRNA has two purposes:
• The mRNA is used in REPLICATION to make more viral DNA.
• The mRNA is transported into the cytoplasm from the nucleus and
undergoes translation to form LATE PROTEINS.
5.) All the materials have been made, and assembly of new viruses occurs. Part of
the late proteins are capsid proteins, which surround the newly made DNA to
form a new nucleocapsid. The other part are envelope proteins that form on
the nucleur membrane.
6.) As the nucleocapsid is complete, it exits the nucleur membrane, taken some
membrane with it, which has the envelope proteins. Now the nucleocapsid has
a lipid envelope around it, forming a new Hepatitis B virus. This exits out of
the cell through a channel.
LIFE CYCLE OF A NEGATIVE SINGLE STRANDED mRNA VIRUS (Pg 12)
Rabies and Influenza A are forms of negative single stranded mRNA viruses.
The diagram below shows the life cycle of the virus with these 7 steps:

1.) The virus bonds to the cell surface membrane at specific receptors, and is
taken up into a membrane-enclosed endosome. This process is known as
endocytosis.
2.) Uncoating in the endosome takes place and the viral (-) RNA is released into
the cytoplasm and transported into the nucleus.

In the nucleus, the viral (-) RNA is used in 3 ways:

3.) The (-) RNA is replicated to produce even more copies of (-) RNA.
4.) The (-) RNA goes through transcription to make (+) RNA, which is mRNA.
The mRNA travels out of the nucleus to the cytoplasm and undergoes
translation to make viral proteins. These viral proteins enter into the nucleus
and wrap around the new copies of (-) RNA and form new nucleocapsids.
 5.) The (-) RNA goes through transcription to make (+) RNA, which is mRNA.
The mRNA travels out of the nucleus to the cytoplasm and undergoes
translation to make viral proteins. These viral proteins travel to the
endoplasmic reticulum and further to the golgi body, forming specialised
glycoprotein receptors. These receptors assemble themselves on the cell
membrane.
6.) The nucleocapsid (on the diagram as the Ribonucleoprotein core) exits the
nucleus through pores.
7.) The nucleocapsid recognizes the points where there are viral proteins on the
cell membrane and buds off at these points, taking memr ane with it. This
forms the lipid envelope and completes replication.

LIFE CYCLE OF A RETROVIRUS (Page 13)

HIV-1 is a form of Retrovirus.
The diagram below shows the life cycle of the virus with these 7 steps:
1.) The virus attaches to the cell membrane at protein receptors and binds to the
membrane through fusion. The contents of the virus are released into the
cytoplasm with the viral lipid membrane being integrated into the cell surface
membrane.
2.) One of the enzymes brought in by the virus, Reverse Transcriptase, uses the
RNA strand and creates a complementary DNA strand. This forms a RNA-
DNA double strand.
3.) The RNA strand is removed and only the DNA strand is left. This is then used
to make a complementary DNA strand, eventually resulting in a double
stranded DNA version of the viral genome.
4.) This DNA is transported via Microtubules to the nucleus and moves into the
nucleus. In the nucleus, an enzyme from the virus, INTEGRase,
INTEGRATES the virus DNA into the hosts DNA. This forms a ProVirus.
5.) The Provirus undergoes transcription by the host’s enzymes, distinguishing it
as if it was its own DNA. This forms Viral mRNA.
6.) The Viral mRNA exits the nucleus and undergoes translation on the
ribosomes, creating viral proteins. Some of the viral proteins produced go
through the endoplasmic reticulum and golgi body to
7.) Some of the viral proteins produced assemble around the RNA, forming a
nucleocapsid.
8.) The nucleocapsid buds out of the cell, taking membrane with the membrane
proteins, forming the lipid envelope. As the host cell forms more and more
viruses, the cell eventually dies as its resources and membrane are exhausted.