Herpes Flashcards
What are the three subgroups of herpes virus?
Alpha
Beta
Gamma
What type of herpes virus causes cold sores?
One
What type of herpes virus causes genital herpes?
II
What types of herpes virus are oncogenic?
4 & 8
What type of herpes causes shingles and chicken pox?
3
What is the only protein expression in latent herpes?
LATs - may help to remain latent?
Are herpes viruses DNA or RNA?
DNA
Where does herpes replicate when it first enters the body?
Epithelial cells
What are the three antivirals used to treat herpes symptoms?
Acyclovir, famacyclovir and valacyclovir
What is acyclovir and analogue of?
Guanosine
Is acyclovir a pro-drug and if so then how is it made active?
Yes and by viral thymidine kinase
How does acyclovir work?
Lacks the ribose moiety and so causes chain termination
What is valacyclovir?
Esterfied version of acyclovir
Greater oral bioavailability
What the famacylovir?
A pro-drug of penciclovir
Guanosine analogues
What future drug therapies are there?
Helicase-primate inhibitors
What do helicase-primate inhibitors do?
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
Why is helicase primase ideal for antiviral strategy?
Multiple enzyme activities
When are infants exposed to HSV?
At delivery in the birth canal
What can neonatal HDV manifest as?
Skin and eye diseases - leads to cognitive impairment, severe neurological disease and organ dysfunction and death,
What is varicella zoster virus?
Causes chicken pox in childhood
Herpes zoster is shingles in later life
What is nerve damage caused by herpes?
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.
What are the new antivirals against varicella zoster virus?
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.
What can be used to treat the pain?
Opioid analgesics and tricyclic antidepressants
What is KSHV?
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
Can HAART therapy help with KSHV?
Variable - dependent in burden of existing disease
How do KSHV work?
Induces vascular endothelial growth factor pathway
Bevacizumab - humanised monoclonal antibody which can be used to block vascular endothelial growth factor A
What do KSHV tumours express?
C-kit (tyrosine kinase receptor that regulates intracellular processes such as cell growth)
Inhibited by imatinib
