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Virology

Early virus treatment

Variolation =

early attempt at

vaccination –

people would

inhale dried crust

of pustules of

smallpox

survivors

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Tobacco Mosaic Virus

Human Immunodeficiency Virus

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Viral Structure

Overall shape:

1. Helical – spiral

2. Icosahedral – 20 sides,

each of which is an

equilateral triangle

3. Complex:

combination of 1+2

Helps determine host range (types of hosts infected) and

tissue tropism (cell/tissue type that can be infected)

Viral Components

1. Genome – DNA or RNA – single-

stranded or double-stranded

2. Capsid – protein shell around the

genome, protects it; gives shape

to the virus

3. +/- Envelope: fatty layer around

some viruses; usually acquired

during exit from the host cell

4. Spike proteins: project through the

envelope (if present); usually aid

in attachment

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Viral Cultivation

1. Embryonated eggs – used to grow

polio and influenza viruses

2. Whole animals – rabbits have

been used to grow rabies virus

3. Organs – livers are used to

grow hepatitis viruses

4. Cell culture – petri dish with a

layer of cells in it; can use

living cells or cancer cells

(“immortal cell line”)

CPEs = cytopathic effects

NORMAL GIANT CELL FUSIONS Fragmented / misshapen

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Viral Replication VIRION = complete assembled

virus particle outside the host cell

1. Attachment: virus attaches to host

cell, uses spike proteins, capsid

proteins, or envelope

2. Penetration: Genome+Capsid enter

the host cell

3. Uncoating: capsid releases genome

4. Biosynthesis: virus genome directs

the synthesis of new virus parts

using the host cell “machinery”

5. Assembly: new virus parts self-

assemble spontaneously

6. Exit: virus leaves the host cell; may

acquire envelope; may kill host

Burst time- attachment to

exit (~45 minutes)

Burst size – 100 new

viruses made per cell

VIRUS Replication (Bacteriophage)

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Entry into Host Cell Replication

Virus Replication (HOST = Animal cell)

Proviruses

Some viruses can exist as proviruses

Strategy for “hidden replication”

Virus inserts a copy of its genome into

the host cell chromosome, gets copied

along with host cell chromosome

during replication

Immune system can’t detect it !!

Exist for long periods of time

(HERPES / HIV)

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Viral Nomenclature/Classification

Usually based on replication strategy

(David Baltimore) Can be based on tissue

type infected:

1. Pneumotropic

(lungs/respiratory tract)

2. Dermotropic (skin and

underlying layers)

3. Viscerotropic (organs

and blood stream)

4. Neurotropic (brain and

central nervous system)

Viral Detection

ELISA: detects patient antibodies

(proteins made by immune

system in response to microbes)

PCR: detects genome of virus

Western Blot: detects viral

proteins (spike/capsid/envelope)

HAI Test: next slide

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The Hemagglutination-Inhibition Test

Viral Plaques !!

Areas on a petri plate full of

bacteria where the bacteria

have been killed by the virus

“clear zones”

Can be used to count viruses

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Anti-Viral Agents/Inhibitors

I. Synthetic Drugs:

A. Base analogues – resemble A/T/C/G

(nucleotide bases of DNA); virus tries to

incorporate them into new virus genomes,

premature termination of replication

B. Viral protein inhibitors –stop one enzyme

made by the virus --

1. reverse transcriptase inhibitors stop the

viral enzyme that makes DNA from RNA;

2. protease inhibitors – stop protease enzymes

that allow virus to make correct capsids

II. Body Defenses

Antibodies -- proteins made by B cells (type of White Blood cell)

– attach to viruses and clump them up for phagocytic removal

T cells – recognize and destroy virus-infected cells

Interferons – proteins made by infected cells; released and signal

other nearby cells to get “ready” for viral attack

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Interferon

Viral vaccines

A. Inactivated – use dead

viruses

B. Attenuated – use live but

weak viruses, replicate too

slowly to cause disease

C. Subunit – made by

biotechnology, comprised of

virus proteins but no live

virus

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Physical and Chemical agents

Viruses and Cancer

Viruses cause 15% of all human cancers

Can damage or modify DNA of host cell

If they damage the genes that control

cell division / mitosis, cells can become

“tumorogenic”

Background: cancer cells divide rapidly, don’t stop dividing

even they contact surrounding tissue, make cell lose “identity”

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“Oncogenic” viruses

The Formation of a Tumor (Oncogenic) Virus

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Origin of Viruses

1. Regressive hypothesis: viruses came

from bacteria that lost functions /

genes needed for independent life

2. Progressive hypothesis : viruses came

from DNA plasmids that gained genes

for capsid production

Which Is Correct ??

Nobody knows

Viral Evolution: where do new viruses come from ?

1. Mutation

2. Recombination: different

viruses exchange genetic

material

3. “Jump Species”: viruses

move from animals to

humans

(cowpox smallpox)

(SIV HIV)

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Virus-like Agents

1. Viroids

2. Prions

“Viroids”

RNA particles (no capsid); cause 12 or more plant diseases

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Prions !

Mad Cow

Disease (BSE)

Usually exist as normal brain proteins; some can lose their shape

and become infectious cause other brain prions to lose shape

(DEADLY CHAIN REACTION)

Can kill brain tissue and cause fatal brain diseases (spongiform

encephalitis – brain tissue eventually looks like a sponge)