HSV (Herpes) Flashcards
Structure of HSV
ds DNA
enveloped with lipids
Important proteins of HSV
- Glycoproteins (gpB and C)
- DNA polymerase
- thymidine kinase: can mono-phosphorylate nucleosides
- ICP47: inhibits MHC class I presentation
HSV replication in cells
- Glycoproteins bind to cell surface
- triggers fusion of envelope
- capsid travels to nucleus and releases its genome
- dsDNA forms episome
- mRNAs express proteins including DNA polymerase, thymidine kinase and ICP47
- Viral linear dsDNA replicated
- late mRNAs express structural proteins that package new genomes
- virion assembled
Effect of HSV on cells
- replication can induce cell death
- vesicle/ulcer formation due to loss epithelial
HSV 1 vs 2
1: Typically causes above the waist spread by saliva
2: below the waist, genital or neonatal herpes
Innate defences induced by HSV
- infected epithelial cells produce IFN beta
- PAMP-PRR interactions cause MF and DC produce type 1 interferons (esp. IFN alpha)
- induce anti-viral state in neighbouring cells
activate NK cells which target infected cells
Adaptive immune response
A slow response
CD8+ cells are most important in controlling infection, and cluster around ganglia dorsal root cells, but is slow because of ICP47
Maternal antibodies can be protective but less important
Acyclovir
- A guanosine analogue
- Nucleosides have no phosphate group and lacks the 3’ hydroxyl group that is required to form DNA polymer > chain terminator
Can be phosphorylated to become a nucleotide by thymidine kinase and cellular enzymes
Primary vs secondary infections of HSV
IgG higher than IgM in secondary infections, and lower viral load
HSV latency
spreads from epithelial cells to dorsal root ganglia (trigeminal ganglia for 1 and sacral for 2)
HSV maintained as episome without replication
sent back up sensory nerves for reactivation
Wy does HSV persist in neurons
low MHC class I expression
- ICP47 inhibition
- low expression of viral proteins
