Basic Virology

Slackers Facts by Mike Ori

Disclaimer

The information represents my understanding only so errors and omissions are probably rampant. It has not been vetted or reviewed by faculty. The source is our class notes.

The document can mostly be used forward and backward. I tried to mark questionable stuff with (?).

If you want it to look pretty, steal some crayons and go to town.

Finally…

If you’re a gunner, buck up and do your own work.

Are viruses alive

It depends an who you ask. Dr. A says yes. They are obligate intracellular parasites that carry

enough genes to reproduce themselves within the defined environment of their host.

How is genetic information encoded in viruses

Genetic information is encoded in either RNA or DNA depending on the virus. It is important to note that viruses do not contain both RNA and

DNA.

What is a virion

A functioning virus particle. Distinguished from an defective particle.

Describe the range of size and complexity in the viraverse (viral-universe - a shiny new word)

Viruses range from the edge of detection with EM to about one-quarter the size of an E. coli.

A,B,C,D Collie omitted for clarity

E. Collie

Chickenpox virus

Pine cona virus

List the patterns of viral growth.

AcuteLatent

ChronicSlow chronic

Set point escape

What is the expected growth pattern for an acute virus.

Initial rise and fall of viremia without resurgence. Done in one.

Describe the expected viremia pattern for a latent virus

Initial acute rise followed by virus free periods punctuated by less intense periods of viremia.

Describe the expected viremia pattern for chronic infection

Initial acute rise in viremia with a fall that does not reach zero. Viremia is detectable in blood

or tissues

Describe the expected viremia pattern with slow chronic infection.

Viremia increases slowly over time.

Describe the viremia associated with set point escape

Really a combination of chronic viremia and rapidly rising slow chronic response. Initial acute infection

followed by a drop in viremia that does not return to zero (aka set point). Eventually, the virus escapes the

immune system in a chronic escalation.

Set point (chronic) Slow chronic-like escape

List the prototypical virus for each pattern

Acute – influenzaLatent – HSV-1

Chronic – Hep BSlow chronic - ??

Set point escape - HIV

What is a viral envelope?

A lipid bilayer derived from host membranes. Most often the source is the plasma

membrane but it may also be the ER/golgi or the nuclear membrane (herpes)

What is the a capsid?

A capsid is a protein structure that surrounds and protects the viral genome. The capsid organizes and provides shape to the virus.

What is nucleocapsid

Nucleocapsid proteins are proteins that organize the genome in enveloped viruses that do not

have an icosohedral core.

What are viral spikes

Proteins that extend from the virus that allow it to interact with its environment.

What are matrix proteins

In enveloped viruses, matrix proteins link the nucleocapsid to the spikes and membrane

Will you take the blue or the red pill coppertop?

What is a capsomere

A capsomere is an aggregation of proteins that forms a modular building component of naked

capsid virus (cubic, icosahedral) and that of enveloped icosahedral virus..

Describe the structure of naked capsid virus.

A naked capsid virus consists of a genome packaged by core proteins surmounted repeating capsomeres organized into an

icosahedral shell from which protein spike protrude.

What is the relative antigenicity of viral structural proteins?

Spikes are more apt to be exposed to the immune system and hence are more likely to

be antigenic. Antibodies directed against spikes should be more efficacious.

What are the functions of spikes

1. Enzymatic (influenza neuroaminidase)2. Fusion with host cells

3. Eliciting immune response

What is tropism

The propensity of a virus to infect specific tissues.

What is the basis for tropism

Access to the tissue and receptors on the tissue

If you were working in a bioweapons lab, what part of the virus would you change to alter its

tropism

The spikes.

What is troopism

An actor’s propensity to form travelling groups.

What is the basis for virus classification. Consider old and new.

Old school: phenotypic and disease characteristics of the virus.

New school: Genetic analysis

Is herpesviridae a fmily, genus, or species designation

A family.XXXviridae

Is simplexvirus a family, genus, or species

GenusXXXvirus

Genius

Is herpes simplex 2 virus a family, genus, or species

A speciesXXX virus

What steps are required for viral infection

1. Attachment2. Penetration3. Uncoating4. Replication5. Assembly6. Release

What are viral penetration mechanisms

Membrane fusion – only in enveloped virusesReceptor mediated endocytosis – naked capsid

virus

Distringuish early and late replication

Classically early replication involves creation of regulatory elements while late replication

involves creation of structural elements and duplication of the genome.

Where do RNA and DNA virus replicate as general rules.

RNA virus replicates in the cytoplasm except orthomyxovirus

DNA replicates in nucleus except for poxvirusRetro viruses replicate in the nucleus.

What is the difference between sense (+) and antisense (-) genetic material

Antisense (-) strands are those whose 5’-3’ is opposite to the mRNA. Sense strands (+) are

oriented in the same direction.

What sense are RNA viruses

RNA viruses can be either + or – depending on the species.

What is the advantage to + stranded RNA

The viral genome is expressed directly by cellular components on entry into the cell with

minimal reliance on viral factors. In concept, + sense can be packed into a smaller suitcase.

What protein do all RNA viruses require for replication

RNA dependent RNA polymerase

Describe when + and – RNA will be present

Both + and – sense RNA is present during genome replication.

Why does pox virus bring an RNA polymerase

Even though pox is a DNA virus, it replicates in the cytoplasm and so has no access to cellular

RNA trascription machinery.

Why would a DNA virus bring a DNA polymerase

1. To control replication without reliance on host replication machinery

2. Because it replicates in the cytoplasm (pox) where host machinery is unavailable

If DNA is normally double stranded, why doesn’t a ssDNA virus fail

Host repair machinery “fixes” the single strand

Describe how RNA viruses circumvent monocystronicity

1. Segmentation2. Viral RNA polymerase stuttering (term?)

3. Proteolysis

How do DNA viruses overcome monocistronicity

Alternative splicing

How are viruses released from the host cell

1. Budding2. Lysis – kill the cell

3. Cytocidal – wait for cell to die

Define productive cycle

Refers to the period of active virus replication

Define non-productive

A cell in which is infected based on the presence of viral genetic material but which produces

no virus

Define temperate

A virus capable of entering a productive phase after a non-productive phase.

Define permissive

A cell that permits production of viral progeny or viral transformation

Define non-permissive

A cell that does not support replication but that may or may not support transformation

When a virus kills the cell before replication can occur, this is known as what?

Abortive replication

Define burst size

Define eclipse phase

The period in which virus particles are not present within cells in an infected cell culture

Define latent phase

The period in which virus particles are not present outside of cells in an infected cell

culture.The phases are confluent at the beginning but

latent phase is longer than eclipse and hence diverge

The number of virions produces per infected cells.

What is the role of interferon alpha and beta

1. Help to limit virus production by altering RNA persistence and translation.

2. Acts to induce CTL and NK cell activity and proliferation(?)

Describe IFN action on RNA synthesis

The presence of dsRNA initiates interferon production. IFN induces the production of a protein kinase and an oligosynthetase which

become active in the presence of dsRNA.The kinase inactivates ribosomes while the

oligosynthetase actives production of an RNase. Thus IFN is a messenger that primes

neighboring cells to halt RNA production should they become infected.

Human polymerases tend to be more tightly controlled than viral polymerases. Why?

Essentially each polymerase have different quality measures. Human polymerases foster genomic stability and slow mutation rates that

prevent cellular derangement. Viral polymerases foster antigenic shift that allows viruses to keep ahead of the immune system

at the expense of increased defective particles.

Describe recombination

When two similar viruses infect the same cell homologous recombination may occasionally

occur that results in the transfer of genetic material between strains..

Describe reassortment

When two strains of a segmented virus infect the same cell, the resulting virus particles

randomly incorporate segments from either virus.

Define antigenic drift

Point mutation in viral genomes that alters viral antigens as a result of point mutations made

by viral polymerase.

Define antigenic shift

Large scale changes made to viral genomes as a result of recombination or reassortment.

Define virulence

The capacity of a virus to produce disease. Note this is dependent on both host and viral

factors.

Which type of viruses are capable of causing transformation

DNA viruses and retroviruses

Define transformation

The conversion of a normal cell into a tumor cell as a result of virus activity.

Define vertical transmission

The spread of disease from mother to child in utero, during parturition, or by lactation