Lec 12 - Persistent viral infections

Question 1

Define persistent viral infection and the 2 types

Answer 1

Virus persists in host long term or for life
1. Latent: virus exits lytic cycle and persists without virion production until reactivated
2. Chronic: lytic replication at low levels

Question 2

What cells does HSV1 and 2 infect and become latent in?

Answer 2

1. Epithelium of skin
2. Sensory epithelial neurons
3. Nuclei of sensory neurons in trigeminal ganglion as episomes

Question 3

What is needed for HSV to establish latency?

Answer 3

1. Block lytic gene expression
2. Block apoptosis and innate immunity
3. Evade or block adaptive immunity

Question 4

What 2 things does HSV encode that control replication?

Answer 4

1. miRNAs to inhibit viral transcription and replication proteins
2. Latency associatd transcripts (LATs) to inhibit apoptosis

Question 5

Describe the typical HSV reactivation cycle

Answer 5

Huge spike in memory cells which decline from T cell suppression

Question 6

Describe the stages of infection and latency in VZV

Answer 6

1. Infect mucosa of upper respiratory tract
2. Spread to lymph nodes and T cells
3. Primary viraemia in blood
4. Secondary viraemia in liver, spleen etc
5. Third viraemia in skin by T cells = rash
6. Infect sensory neurons with latency in dorsal root ganglion
7. Reactivates as shingles

Question 7

Describe the progression of HIV

Answer 7

Initial acute infection persists as CD4+ declines until AIDS then end stage

Question 8

What does HIV use to evade immunity?

Answer 8

1. Mutating epitopes
2. Nef gene inducing FasL expression by T cell, binds Fas and causes T cell death
3. CD4+ T cell depletion

Question 9

How are CD4+ T cells depleted by HIV?

Answer 9

1. CPE
2. Activating uninfected cells = apoptosis
3. Expressing viral pepides on surface for CTL to detect and kill

Question 10

What cancer is cause by HBV and HCV and how?

Answer 10

Hepatocellular carcinoma by prevention of apoptosis.
Progresses from inflammation and cirrhosis