Herpes

Question 1

What are the three subgroups of herpes virus?

Answer 1

Alpha
Beta
Gamma

Question 2

What type of herpes virus causes cold sores?

Answer 2

One

Question 3

What type of herpes virus causes genital herpes?

Answer 3

II

Question 4

What types of herpes virus are oncogenic?

Answer 4

4 & 8

Question 5

What type of herpes causes shingles and chicken pox?

Answer 5

3

Question 6

What is the only protein expression in latent herpes?

Answer 6

LATs - may help to remain latent?

Question 7

Are herpes viruses DNA or RNA?

Answer 7

DNA

Question 8

Where does herpes replicate when it first enters the body?

Answer 8

Epithelial cells

Question 9

What are the three antivirals used to treat herpes symptoms?

Answer 9

Acyclovir, famacyclovir and valacyclovir

Question 10

What is acyclovir and analogue of?

Answer 10

Guanosine

Question 11

Is acyclovir a pro-drug and if so then how is it made active?

Answer 11

Yes and by viral thymidine kinase

Question 12

How does acyclovir work?

Answer 12

Lacks the ribose moiety and so causes chain termination

Question 13

What is valacyclovir?

Answer 13

Esterfied version of acyclovir

Greater oral bioavailability

Question 14

What the famacylovir?

Answer 14

A pro-drug of penciclovir

Guanosine analogues

Question 15

What future drug therapies are there?

Answer 15

Helicase-primate inhibitors

Question 16

What do helicase-primate inhibitors do?

Answer 16

UL9 binds to origin and causes a bend in the DNA - stem loop & unwinding of DNA
ICP8 is then recruited to UL9 leading to the recruitment of other 5 essential proteins to the replication fork
DNA polymerase begins DNA synthesis
Once new strand growth progresses the circular replication structure is nicked to form the rolling circle mechanism

Question 17

Why is helicase primase ideal for antiviral strategy?

Answer 17

Multiple enzyme activities

Question 18

When are infants exposed to HSV?

Answer 18

At delivery in the birth canal

Question 19

What can neonatal HDV manifest as?

Answer 19

Skin and eye diseases - leads to cognitive impairment, severe neurological disease and organ dysfunction and death,

Question 20

What is varicella zoster virus?

Answer 20

Causes chicken pox in childhood

Herpes zoster is shingles in later life

Question 21

What is nerve damage caused by herpes?

Answer 21

Post-herpetic neuralgia - nerves in the dermatitis area of the skin to send abnormal electrical signals to the Braun. These may ℅ very excruciating pain and be present for months, years etc.

Question 22

What are the new antivirals against varicella zoster virus?

Answer 22

Cidofovir derivatives - selectively inhibits viral DNA polymerase. Requires two phosphorylation steps whereas acyclovir needs 3. Independent of viral phosphatases as can be phosphorylated by cellular kinases.
CMX001 - lipid ester of cidofovir
ASP2151 - helicase primase inhibitor
Bi cyclic pyrimidine nucleoside analogues - need activating by virus kinases. (Mono and do phosphates) viral thymidine kinase.

Question 23

What can be used to treat the pain?

Answer 23

Opioid analgesics and tricyclic antidepressants

Question 24

What is KSHV?

Answer 24

Kaposis sarcoma (endothelial lineage)
8 & 2 are the oncogenic viruses
2 distinct life cycles
Acyclovir is not phosphorylated by the viral thymidine kinases so cant be used whereas ganciclovir is phosphorylated to some degree

Question 25

Can HAART therapy help with KSHV?

Answer 25

Variable - dependent in burden of existing disease

Question 26

How do KSHV work?

Answer 26

Induces vascular endothelial growth factor pathway

Bevacizumab - humanised monoclonal antibody which can be used to block vascular endothelial growth factor A

Question 27

What do KSHV tumours express?

Answer 27

C-kit (tyrosine kinase receptor that regulates intracellular processes such as cell growth)
Inhibited by imatinib