Questions from S 18 Flashcards
In 2020 the Nobel prize was awarded for work on HCV
Who shared the award?
Houghton
Rice
Alter
Which scientist linked HPV to cancer?
German - Harold zur Hausen
in 1960s - not acknowledged til 1990s
2008 HPV immunisation program started in UK
What is the Australia antigen?
HBsAg
Named Australia antigen after first discovery in aboriginal people in Australia
Discovered by Baruch Blumberg
Where was HEV first discovered?
First discovered in Afghanistan when Russian soldier became unwell. Diagnosed by electron microscopy
Then realised that years earlier this had been occurring in Kashmir
What is unique about HEV infection?
Higher mortality in pregnancy - 25% mortality
What is mechanism of action of aciclovir?
Which enzymes take part in this?
Phosphorylated to monophosphate form by viral Thymidine Kinase
Phosphorylated to bi/triphosphate form by cellular kinase
Acts as a nucleoside analogue, competitively inhibiting viral DNA polymerase, and also causing chain termination
Actions:
1. irreversibly inhibits viral DNA polymerase directly
2. added to growing chain, causing chain termination
How to test for aciclovir resistance in the lab?
Genotypic - e.g UL23/ UL30
Whole genome sequencing
Phenotypic - plaque reduction assay
How does a plaque reduction assay work?
Grow live virus in fibroblast cell culture - observe cytopathic effect, and formation of plaques
Add aciclovir at different concentrations, which inhibits viral growth
Note which concentration results in 50% plaque reduction.
This is the PRNT50
What are common aciclovir resistance mutations?
UL5 - helicase primase - virus no longer needs this enzyme for DNA unwinding
UL23 - Thymidine Kinase - aciclovir no longer phosphorylated to active form
UL30 - DNA polymerase - aciclovir can no longer bind to DNA polymerase
UL23 Thymidine kinase mutation
What are the different ways to describe this mutation?
TKN - negative - complete deficiency in viral TK. So aciclovir cannot be phosphorylated to active form
TKP - partial. Partial deficiency in viral TK
TKA - altered - alteration of TK means aciclovir cannot be phosphorylated to active form
TK mutation means virus usually less fit than wild type virus. So less likely to transmit
Patient with drug resistant HSV infection
What do you do?
Clarify why resistance occurred:
poor compliance
poor absorption
wrong dose
immunosuppressed
Increase dose
Increase frequency
Increase duration
Switch to IV
Switch to alternative drug class
Check HIV test
HSV drug resistance
Name alternative drugs, their target, and the dose
Cidofovir
DNA polymerase
5mg/kg once a week
Foscarnet
DNA polymerase
40mg/kg TDS for HSV
(60mg/kg TDS for CMV)
Maribavir only used in CMV
