Herpesvirus and Latency

Question 1

Alphaherpesvirinae

Answer 1

HSV I, 2

varicella zoster virus

Question 2

Betaherpesvirinae

Answer 2

CMV

HHV6, roseola

Question 3

Gammaherpesvirinae

Answer 3

EBV, HHV4

KSHV, HHV8

Question 4

Alphaherpesvirus Genome Organization

Answer 4

• most of genes assoc. w/ lytic infection

- latent assoc. domain

Question 5

HSV Latency-LAT region

Answer 5

• separated from lytic genes by chromatin insulator
• region of the chromosome which blocks activation of insulated region
• lies b/w promoter and enhancer of gene

Question 6

HSV Latency-LAT transcript

Answer 6

• predominant viral transcript produced in latency-non coding
• mechanism of action still controversial
• microRNA theory-precursor gives rise to 4 miRNAs, one of these is antisense to ICP0

Question 7

Role of ICP0

Answer 7

• Tc activator
• involved in HSV reactivation
• repressed during latency

Question 8

Mechanisms of ICP0 latency repression

Answer 8

• LAT-RNA mediated silencing
• suppression by ICP4
• LAT RNA mediated altering of chromatin

Question 9

LAT expression involved in

Answer 9

• genome silencing

- inhibition of apoptosis

Question 10

Diseases of EBV

Answer 10

-infectious mononucleosis
Various cell proliferative diseases
-Nasopharyngeal carcinoma (proliferation of epithelial cells)
-Burkitts Lymphoma (proliferation of B cells, myc translocation to locus is primary cause of disease)
-Hodgkins disease (proliferation of B cells, genetic mutations in JAK-STAT and NF-kappaB)
-Gastric carcinoma (epithelial cells)
*EBV is often cofactor of disease, not primary cause)

Question 11

EBV Latency-EBNA

Answer 11

• epstein barr nuclear antigen

- important for maintenance of EBV episome, host gene regulation and transformation

Question 12

EBV Latency-LMPs

Answer 12

• latent membrane proteins
• integral membrane proteins which modulate cell signalling
• LMP2a provides survival signal normally given by BCR-allows EBV infected B cells to transit to germinal centre

Question 13

BCR1

Answer 13

• IL10 homolog (Th2 cytokine, suppresses Th1 responses)
• reduces mRNA levels of TAP1 and bli/LMP2 (immunoproteosome subunit-regulation of CD8+ T cell responses)
• ->swings balance toward Th2 type

Question 14

LMP1

Answer 14

• allows infected B cell to survive

- provides cell survival signal in the absence of ligand

Question 15

LMP2

Answer 15

recognizes antigen

-allows infected B cell to survive in the absence of external stimuli