Chapter 13

Viruses, Viroids and Prions

• Adolf Mayer, 1886
– tobacco mosaic disease (TMD) transmissible

• Dimitri Iwanowski, 1892

– Filtered sap still caused TMD
– contagious fluid or filterable agent

• Walter Reed,1901
– Yellow Fever
• Felix d’Herelle, 1917
– Bacteriophage
– Suggested phage therapy

• 1930’s, term virus introduced and

electron microscopy invented

• Wendell Stanley, 1935

– Isolated tobacco mosaic virus
[INSERT FIGURE 13.4]
• Viral Features
– Obligate intracellular pathogen
– Host range
• highly specific or generalists
– DNA or RNA
– Protein coat
– Surface proteins highly susceptible to mutations
– Cause synthesis of specialized structures to
transfer viral particles to other cells
• Virion
– complete, fully developed, infectious viral particle
– Living or non-living entities?????
 Viral Classification

• Oldest system based on symptomology

• International Committee on Taxonomy of Viruses
(ICTV), 1966
– Describe viruses as elementary bio-systems
– Classified into orders, families, genera and species
– Over 1,500 officially recognized species
• 3 primary means of classification:
– Nucleic acid

– Replication strategy

– Morphology of protein coat (capsid)

 Helical Viruses

Polyhedral Viruses
• Viral Envelope
– Acquired from host cell
– Phospholipids and proteins
– Some glycoproteins are virally coded spikes
– Often play role in host recognition
Critical Swine Flu prevention tip:
Don't DO this!
Complex Viruses
[INSERT FIGURE 13.5]
 Viral Taxonomy

• Order –virales

• Family –viridae

• Genus – virus

• Species
– Common names
– Subspecies designated by a number
 Viral Taxonomy

• Retroviridae– family
– Lentivirus – genus
• Human Immunodeficiency Virus– species

• Herpesviridae
– Simplexvirus
• Human herpesvirus 1, HHV 2, HHV 3
 Isolation and Cultivation of Viruses

• Viruses must be grown

in living cells
– Cytopathic effects
• Animal viruses
may be grown in
living animals or
in embryonated
eggs
• Animal & plants viruses may be grown in cell cultures
– Primary cell lines
– Continuous cell lines (transformed cells )
 Virus Identification

• Serological tests
– Detect antibodies against viruses in a patient
• Nucleic acids
– RFLPs
– PCR
 Multiplication of Bacteriophages

• Lytic cycle Phage causes lysis and

death of host cell

• Lysogenic cycle Temperate phages

incorporate DNA into host
DNA (prophage)
 Lytic Cycle

• Attachment Phage attaches by tail fibers to

host cell
• Penetration Phage lysozyme opens cell wall,

tail sheath contracts to force tail

core and DNA into cell
• Biosynthesis Production of phage DNA
and proteins
• Maturation Assembly of newly synthesized
phage particles
• Release Phage lysozyme breaks cell wall
[INSERT FIGURE 13.8]
One-step Growth Curve
Lysogenic Cycle
• 3 Important results of lysogeny
– Immunity to re-infection
– Phage conversion
– Specialized transduction
 Specialized Transduction
Prophage gal gene Bacterial DNA

1 Prophage exists in galactose-using host

(containing the gal gene).
Galactose-positive
donor cell gal gene
2 Phage genome excises, carrying
with it the adjacent gal gene from
the host.

gal gene 3 Phage matures and cell lyses, releasing

phage carrying gal gene.

4 Phage infects a cell that cannot utilize

galactose (lacking gal gene).
Galactose-negative
recipient cell
5 Along with the prophage, the bacterial gal
gene becomes integrated into the new
host’s DNA.

6 Lysogenic cell can now metabolize

galactose.
Galactose-positive recombinant cell
 Multiplication of Animal viruses

• AttachmentViruses attaches to cell membrane

• PenetrationBy endocytosis or fusion
• Uncoating By viral or host enzymes
• Biosynthesis Production of nucleic acid and
proteins
• Maturation Nucleic acid and capsid proteins
assemble
• Release By budding (enveloped viruses)
or rupture
• Attachment of animal viruses
– Chemical attraction
– No tails or tail fibers
– Glycoprotein spikes or other attachment molecules
• Replication of Animal Viruses
– Biosynthesis
• Each virus requires different strategy depending on
its nucleic acid
• DNA viruses often enter the nucleus
• RNA viruses typically replicate in cytoplasm
• Must consider:
– What serves as template for replication and how
mRNA is transcribed
 Multiplication of DNA Virus
Papovavirus 1 Virion attaches to host cell
7 Virions are released
Host cell
DNA
Capsid

DNA 2 Virion penetrates

cell and its DNA is
6 Virions mature Cytoplasm
uncoated

Capsid proteins

mRNA

5 Late translation;
capsid proteins
are synthesized

3 Viral DNA penetrates host nucleus

4 Late transcription; Early transcription and translation;
DNA is replicated enzymes are synthesized
Multiplication of RNA Virus

[INSERT FIGURE 13.13]

 Multiplication of a Retrovirus
Reverse Capsid
transcriptase DNA

Virus Two identical + stands of RNA

1 Retrovirus penetrates
Host host cell.
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host Reverse
cell, acquiring transcriptase
an envelope as
it buds out.
Identical Viral RNA 2 Virion penetrates
cell and its DNA is
strands of
uncoated
RNA
4 Transcription of the
provirus may also occur,
Viral proteins producing RNA for new
retrovirus genomes and
RNA that codes for the
RNA
retrovirus capsid and
envelope proteins.
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
Provirus
• Assembly and release of animal viruses
• Most DNA viruses assemble in and are released
from nucleus into cytosol
• Most RNA viruses develop solely in cytoplasm
• Enveloped viruses cause persistent infections
• Naked viruses are released by exocytosis or may
cause lysis and death of host cell
 Viruses and Cancer

• Oncogenes transform normal cells into tumor cells

– Activated by mutagenic chemicals, radiation, viruses
– Causes increased growth, loss of contact inhibition
– Cells tend to be misshapen and exhibit chromosomal
abnormalities
•Oncoviruses
•Viral DNA integrated into
host DNA
•Induces tumors
 Oncogenic Viruses

• Oncogenic DNA • Oncogenic RNA

Viruses viruses
– Adenoviridae – Retroviridae
– Herpesviridae • DNA
– Poxviridae • HTLV 1
– Papovaviridae • HTLV 2
– Hepadnaviridae
• Latent Viral Infections
– Virus remains dormant in asymptomatic host cell
for long periods
• Cold sores, shingles

• Persistent Viral Infections

– Disease progresses slowly over a long period,
generally fatal
• Subacute sclerosing panencephalitis
(measles virus)
• Plant Viruses
– Plant viruses
enter through
wounds or via
biting insects
– May be
transmitted in
pollen

• Viroids
Potato Spindle Tuber Viroid
– infectious naked
RNA
 Prions

• Proteinaceous infectious particle

• Inherited and transmissible diseases
• Spongiform encephalopathies
– Sheep scrapie, Creutzfeldt-Jakob disease, Gerstmann-
Sträussler-Scheinker syndrome, fatal familial insomnia,
mad cow disease
PrPC, normal cellular prion protein
PrPSc, scrapie protein
 [INSERT FIGURE 13.23]

scrapie proteins accumulate in brain cells forming large vacuoles