Herpes Virus

Question 1

What type of viruses are herpesviruses?

Answer 1

Double stranded DNA viruses

Question 2

How many herpes viruses cause disease in humans

Answer 2

8

Question 3

Give 4 structural features of herpes virus

Answer 3

1. Core containing the large ds genome surrounded by a proteinaceous core
2. The complex icosahedral capsid surrounds the core
3. Outside the capsid is the tegument, a protein-filled region
4. On the outside of the particle is the envelope which contains numerous glycoproteins

Question 4

What are the two distinct life cycles?

Answer 4

1. Lytic which produces infectious virions causing cell destruction and allowing the virus to spread
2. Latent infection allows the ability to persist indefinitely

Question 5

What are the 8 subfamilies of herpesvirus?

Answer 5

Gammaherpesvirinae
Betaherpesvirinae
Alphaherpesvirinae

Question 6

What are the three groups in alphaherpesvidinae?

Answer 6

HSV1
HSV2
VZV

Question 7

What are the three groups in betaherpesvirinae?

Answer 7

HHV7
HHV6
CMv

Question 8

What are the two groups in gammaherpesvirinae

Answer 8

KHSV

EBV

Question 9

What is the result of HSV1/2?

Answer 9

1 is common cold sore and 2 is genital herpes

Question 10

Which group of herpes viruses are the largest?

Answer 10

Beta, associated with Alzheimer’s lesions

Question 11

Which group have oncogenic potential?

Answer 11

Gamma

Question 12

Which sub-family has has the most restricted host range and which has the most variable host range and why?

Answer 12

Most - gamma, replicate in lymphoblasoid cells, lytic in epithelial cells. Latent in T or B cells
Least - alpha, spread rapidly, efficient cell destruction. Latent infection in sensory ganglia

Question 13

How many gene products does HSV code for?

Answer 13

80

Question 14

How are the two segments in the genome linked?

Answer 14

Covalently, flanked by inverted repeats

Question 15

What do the inverted repeats allow?

Answer 15

Rearrangements of the unique regions, genomes exist as a mixture of 4 isomers.

Question 16

How many genes are pathogenic?

Answer 16

40

Question 17

What does virus entry require?

Answer 17

1. gB and gC glycoproteins bind to cell surface proteoglycans
2. Attachment is then stabilised by gD binding to herpesvirus entry mediators, Hve A, B and C.
3. pH-independent fusion of the viral envelope with the cell plasma membrane
   gB, gD, gH and gL are involved.

Question 18

How are viral protein groups expressed?

Answer 18

Temporal cascade fashion. IE switches on the expression of viral genes which include enzymes required for DNA metabolism and replication so structural genes can form the virus particle

Question 19

How is IE expression initiated?

Answer 19

Recruitment of cellular factors to IE promoters enhanced by the tegument protein VP16 or aTIF

Question 20

What does VP16 interact with?

Answer 20

Oct-1, HCF, TFIIB and TFIID

Question 21

What do IE genes do?

Answer 21

Regulate E and L gene expression as well as providing cellular environment conductive to viral synthesis

Question 22

What is ICP0?

Answer 22

Promiscuous transactivator of all classes of HSV genes, interacts with cellular factors allowing transactivation of early promoters. Disrupts cellular ND10 (sites of cellular transcription) providing an environment for conducive viral synthesis. Prepares the cell for replication

Question 23

What is ICP4?

Answer 23

Essential for transactivating all early and late genes, interacts with cellular factors, allowing recruitment to early promoter

Question 24

What is ICP22?

Answer 24

Enhances expression of ICP0

Question 25

What is ICP27?

Answer 25

Transactivates late genes, acts at a post transcriptional level. Stabilise viral mRNA and transports it from nucleus enhancing translation

Question 26

What is ICP47?

Answer 26

interferes with host immune response: affecting MHC class I presentation

Question 27

What is ND10?

Answer 27

Promyelocytic leukemia nuclear bodies, discrete nuclear foci that contain several cellular proteins involved in diverse processes such as transcription, chromatin structure, DNA repair and apoptosis

Question 28

Name 7 genes which are essential for virus genome replication

Answer 28

1. UL9 origin binding protein 2. ICP8 ss DNA binding protein 3. UL5/UL8/UL52 helicase/primase complex 4. UL30/UL42 DNA polymerase

Question 29

Describe herpes virus genome replication

Answer 29

1. UL9 binds to one of the 3 replication sites and the genome circularises 2. In conjugation with ICP8 the DNA bends forming a stem-loop and unwinding the DNA 3. Helicase-primase binds the ssDNA and synthesises RNA primers 4. Viral polymerases bind RNA primers and start the synthesis of DNA

Question 30

What form is the genome replicated in?

Answer 30

A rolling circile intermediate forms Concatemeric strands

Question 31

How are viruses assembled?

Answer 31

Procapsids are formed first around the scaffold proteins. These are digested away so the capsid can incorporate the DNA through a portal. The terminase proteins UL15, UL28 and UL33 act as an ATP-dependent pump that drives the DNA into the procapsid and cuts the concatemeric DNA

Question 32

How does the virus exit the nucleus?

Answer 32

1. Budding at the inner nuclear membrane leads to presence of enveloped primary virions in the perinuclear cleft 2. Fusion of the primary envelope with outer nuclear membrane 3. Pass through the outer membrane where the primary envelope membrane is lost. 4. Associates with tegument proteins and bud into golgi-derived exocytotic vesicles

Question 33

How do viruses access the neurone?

Answer 33

Through the axon-terminal, removes the tegument layer

Question 34

What is the role of LAT?

Answer 34

Keep the genome silent and avoid host immune surveillance, prevent apoptosis. Processed to expressed 4 miRNAs which prevent the expression of lytic regulatory proteins (ICP0)

Question 35

How does a latent episome reactivate?

Answer 35

Reorganise its chromatin and accumulate HCF-1 and VP16

Question 36

What is acyclovir?

Answer 36

Antiviral which specifically targets the herpes DNA replication mechanism

Question 37

How does acylovir interrupt DNA replication

Answer 37

Thymidine kinase phosphorylates acyclovir. It is incorporated into the DNA and prevents chain elongation.

Question 38

What are helicase-primase inhibitors?

Answer 38

Prevents progression through helicase of catalytic cycles