Viral Pathogenesis

Question 1

Explain the effects of tissue tropism, virulence and host responses on the nature of viral disease.

Answer 1

Tropism is determined by:

• access to the tissue in which it can replicate
• receptors required for virus binding and entry
• expression of host genes required for virus infection and production of new progeny virus
• relative failure of host defenses.

Tropism (tissue specificity) can drive virus population variants among or within individuals, particularly in viruses with highly error prone replication systems.

Some viral disease is actually mediated by the host immune response to the infection. These include:

• Antibody mediated (immune complex diseases)
• Cell mediated responses (rash, fever and malaise)
• Autoimmunity (possibly due to cross-reactivity with virus)
• Transient immune modulation such as immune suppression.

Question 2

Compare and contrast acute local disease versus acute systemic disease in incubation periods, virus shedding and transmission, host responses, and likelihood of re-infection.

Answer 2

Local

• 1-3 days incubation
• Shed from initial site
• Make IgA
• These viruses are highly mutable, so re-infection likely

Systemic

• 10-21 days incubation
• Shed from multiple or distal site
• Make IgA AND IgG
• Lifelong immunity

Question 3

Describe the expected outcome of viral infection and disease in a healthy host versus an immune compromised host, including symptoms, shedding and transmission, and length of primary infection.

Answer 3

It’s all worse.

Question 4

Detail two differences between persistent and latent infection.

Answer 4

Generally PERSISTENT infection refers to ongoing virus production (e.g. HepB), while LATENT infection refers to a true latent or dormant state in which the virus is not replicating (e.g. EBV)

Persistent:
- continued production of new virus over a long period of time.

Latent:

• virus genome is relatively silent
• little gene transcription in most infected cells
• little to no disease in a healthy host for a long time, in many cases for life.

Slow:

• No symptoms on initial infection
• Long incubation period
• May or may not induce an immune response
• Eventual disease is followed by progressive deterioration and death.

Latent virus differs from dead-end infections (those caused by defective virus or which lack the ability to ever produce virus) in that they retain the ability to re-initiate transcription and replication to produce new virus. This process is referred to as reactivation or recrudescence.

Question 5

List the potential outcomes and types of virus diseases, with the contributing factors.

Answer 5

No idea, but here are epidemiological factors:

• spread/transmission
• susceptibility to re-infection
• age dependence
• group/population effects
• seasonality
• immune status of host
• and animal reservoirs.