Lecture 12 - Herpes 2

Question 1

What causes herpesviruses nucleocapsid portal vertex to be a weak spot? What happens if there is a failure in the integrity of the nucleocapsid?

Answer 1

The pressure created inside of the nucleocapsid by the linear dsDNA genome. If the nucleocapsid fails, the viral genome could be released into the cytoplasm

Question 2

What happens when dsDNA is in the cytoplasm?

Answer 2

Multiple dsDNA sensore recognize it and activate antiviral protein STING

Question 3

Describe the mechanism of action for STINGs antiviral activity (6 steps)

Answer 3

1) dsDNA in cytoplasm activates cGAS
2) activated cGAS cyclizes ATP and GTP to form the secondary messenger cGAMP
3) ER-associated STING binds to cGAMP and translocates to the golgi
4) STING activates kinsae TBK1
5) TBK1 phosphorylates and activates interferon transcription factor IRF3
6) IRF3 translocates to the nucleus and activates transcription of interferon genes

Question 4

What are 3 keys features of viral latency?

Answer 4

1) no viral gene products made
2) immune detection of latently infected cells is impaired
3) Viral genome remains intact

Question 5

Why MUST viral genomes remain intact during latency?

Answer 5

In order for latency to be reversible - reactivation

Question 6

Name 2 common features of herpes virus reactivation from latency

Answer 6

1) relaxation of chromatin

2) aided by stress-responsive transcription factors

Question 7

How does relaxation of host chromatin assist in reactivation from latency?

Answer 7

Relaxed chromatin allows the viral genome to be more easily accessed by transcription factors

Question 8

What are the 3 mechanisms that occur in the nucleus to establish latency of herpes viruses?

Answer 8

1) circularization of its linear genome
2) rapid association of viral genome with histones: compaction of vDNA
3) tethering of viral genome to host chromatin

Question 9

What occurs when viral DNA associates with histones in the nucleus?

Answer 9

it compacts

Question 10

Describe the mechanism for stress-dependent KSHV reactivation from latency

Answer 10

1) the stress sensor IRE1 senses misfolded proteins in the ER and dimerizes
2) stress-induced dimeric IRE1 produces a transcription factor
3) the transcription factor activates transcription of genes associated with ER expansion, protein folding chaperones and protein degradation (helps to make the ER work better)
4) the transcription factor can also bind the KSHV episome and activate lytic replication