Latent and Persistent Infections

Question 1

How does tissue damage develop in acute viral infections?

Answer 1

Overactive immune response induces tissue damage.

Question 2

What are the primary differences between acute and chronic infections?

Answer 2

1. The virus isn’t cleared (for months - to a lifetime)
2. Initial robust immune response is subdued to prevent immunopathology. Maintains adequate control of the virus activity.
3. The immune response of the host is set to a higher activation state.

Question 3

What are the two types of viral lifestyles that are present during chronic infections?

Answer 3

1. Latent (quiescent) infection
2. Persistent replication

Question 4

What is the prototype for latent viral infection?

Answer 4

Herpesviruses

Question 5

In the Herpesvirus lytic replication cycle:

1. Where does the virus go first for replication?
2. What degrades host mRNA?
3. What does viral transcription factor VP16 do?
4. What shape is the viral DNA initially? Does it change?

Answer 5

1. Its DNA is transported to the nucleus
2. Viral vhs
3. Initiation of viral gene transcription
4. Initially linear, then circularizes before transcription

Question 6

In the Herpesvirus lytic replication cycle:

1. What transcribes HSV alpha genes?
2. How are beta genes activated?
3. What triggers expression of gamma viral genes?
4. What is the role of many gamma viral gene products?

Answer 6

1. Host RNA polymerase II
2. Transactivation by alpha gene products
3. Viral DNA synthesis
4. Structural components of the virion

Question 7

In the latent life cycle of herpesviruses:

1. What steps are shared between lytic and latent life cycle?
2. How is viral DNA maintained? What is the benefit of this?
3. What is the benefit of limited expression of viral genes?

Answer 7

1. Viral attachment and entry, Transport of DNA to nucleus, Circularization of DNA
2. Maintained as an extra chromosome, allows viral genome to survive cellular division
3. Helps maintain the viral episome and prevent loss during cell division

Question 8

What are the primary advantages to the virus of latent infection?

Answer 8

1. Stealth - infected cells are invisible to the immune response
2. Difficult to eliminate due to impaired therapeutic targeting

Question 9

What are the disadvantages to the virus from latent infection?

Answer 9

1. Spread to naive host is limited
2. Death of a latently infected cell is a dead end

Question 10

How does a latent virus overcome limited transmission to naive host?

Answer 10

The virus can switch from latent life cycle to lytic replication. Dangerous as host cell can be eliminated before infectious virions are produced.

Question 11

How does a latent virus overcome elimination by death of a latently infected cell?

Answer 11

Viral latency is established in long-lived cells

1. Herpesvirus: neurons, memory T and B cells, hematopoietic stem cells
2. HIV: memory T cells

Question 12

1. What is the prototype for chronic persistent virus infection?
2. Is the lifecycle similar or different to latent infections? How?
3. What is the profile of virus specific T cells in such an infection?
4. What is T cell exhaustion?

Answer 12

1. Hepatitis C virus
2. It is different, limited to a single life cycle: lytic replication only
3. They are constantly stimulated with high levels of virus antigens
4. T cells upregulate inhibitory receptors that attenuate signaling downstream of T cell receptor. This leads to loss of antiviral function and T cell death.

Question 13

What is an example of a combination of latent and persistent virus infection?

Answer 13

HIV