L20 - Patterns of viral infection

Question 1

What are the 7 stages of the viral life cycle?

Answer 1

Attachment, penetration, uncoating, hijack host functions, replication, assembly, release

Question 2

Viruses are always obligate intracellular parasites. True/False?

Answer 2

True

Question 3

What are the natural barriers to infection?

Answer 3

Skin, mucus

Question 4

What are the components of the innate response to viral infection?

Answer 4

Interferons, NK cells, macrophages - apoptosis

Question 5

What are the components of the adaptive response to viral infection?

Answer 5

Dendritic cells, CD4+ T-cells, CD8+ T-cells, antibodies

Question 6

3 requirements for initiating an infection

Answer 6

sufficient virus present to initiate an infection, cells at site of infection susceptible/permissive for the virus, local host anti-viral defence mechanism absent or ineffective.

Question 7

Which interferons are produced as part of the innate defence, which cells produce them and what are they triggered by? What is the result?

Answer 7

IFN-alpha and IFN-beta are produced by almost all nucleated cells in response to a viral infection or the presence of dsRNA. As a result, transcription of interferon sensitive genes is activated whose products have antiviral effects.

Question 8

Which classes of antibodies are produced during adaptive defence against viral infections?

Answer 8

IgG, IgA, IgM

Question 9

What are the three main mechanisms of cell-mediated defence (adaptive) with diagram

Answer 9

Non-specific - NK cells releasing perforin (not MHC-restricted)
Specific killing - CD8+ T cells recognise peptides on virally infected cell via TCR complexes and destroy them (MHC-restricted)
ADCC - NK or CD8+ cells activated by antibody binding

Question 10

What 3 factors contribute to successful evasion of host defences

Answer 10

Ability to block innate defences eg herpesvirus, HIV and adenovirus
Rapid evolution of antigenic targets - re-assortment of genome fragments allow surface proteins to be replaced (influenza). High rate of mutation during genome replication (HIV).
Initiation of non-cytopathic infection - delays/avoids immune response eg. papillomaviruses (warts)

Question 11

The adaptive response doesn’t impact viral growth for several days, therefore what are its main two functions?

Answer 11

Final clearance, memory

Question 12

Pathogenic effects are not always a direct result of the virus, what else could cause symptoms?

Answer 12

The active immune response, especially cytokines.

Question 13

Which virus can have a first and second (not common - 1%) round of infection ending in paralysis?

Answer 13

Poliomyelitis. Initially infects GI tract (diarrhoea). May enter bloodstream and infect CNS causing paralysis.

Question 14

Name 4 acute infections commonly associated with epidemics.

Answer 14

Polio, measles, influenza, norovirus

Question 15

What are the 3 types of persistent infection with examples of each?

Answer 15

Chronic (Hepatitis C), latent (Herpes simplex), slow (HIV)

Question 16

Evasion of host responses can be done via 2 main routes:

Answer 16

Avoidance and inhibition

Question 17

How can viruses AVOID the host immune system?

Answer 17

Infect immune privileged sites eg, eyes, brain, CNS where immune surveillance and killing is infrequent.
Down-regulate viral gene expression - so as to avoid detection
Variation of antigenic epitopes eg HIV and hepatitis C

Question 18

How can viruses INHIBIT host immune responses?

Answer 18

Infect the immune system itself (lymphocytes + macrophages)
Production of compounds which mimic immune system regulators
Directly subvert the immune system by inhibiting cytokine action, apoptosis, NK cell lysis and MHC-restricted antigen presentation

Question 19

What 4 general properties characterise LATENT infections

Answer 19

1) Viral genome persists and remains capable of initiating an acute viral infection later on
2) Immune detection is reduced or eliminated
3) Viral and host DNA are replicated together
4) Expression of viral genes involved in virions is absent

Question 20

Describe how herpes simplex virus can cause LATENT infection

Answer 20

Primary infection - affects epithelial cells causing acute cytolytic infection shown as cold sores, sore throat. Latent infection - Some virus passes into CNS and hides in the trigeminal nerve ganglion - asymptomatic as no virus or virion particles are produced.
Reactivation - virus replicates, travels down sensory nerve to infect nose/mouth epithelial cells again

Question 21

Describe the pattern of a SLOW virus infection.

Answer 21

Begins like an acute virus (there are symptoms and virus shedding). Then long phase of no symptoms but there may be bursts of viral replication and shedding. Fatal if left untreated. eg. HIV and measles SSPSE (subacute sclerosing panencephalitis)

Question 22

Describe how measles SSPSE can cause a SLOW infection

Answer 22

Normally acute infection may switch to persistent disease via viral dissemination and immunosuppression. Virus enters brain via infected lymphocytes causing progressive neurological deterioration and eventually death. Effects appear up to 10 years after initial infection.