Viral Persistence Flashcards
What is the decision point following acute infections?
Either goes into chronic infection or the immune system overcomes the virus
What is annelovirus?
A negative strand DNA virus that is in all of us and is a chronic virus but doesn’t really cause any disease
What is interesting about ERVs (endogenous retroviruses)?
They are retroviruses that have integrated themselves into our genomes, and got into the Germline at some point, about 9% of our genomes are ERVs.
What persistent infections occur in neuronal cells/CNS?
HSV-1
JC virus
What persistent virus infections occur in the liver?
HBV
HCV
What persistent virus infections occur in immune cells?
HIV-1
HTLV
HHV6
EBV
What are the two ways of viral genome being maintained in the cell?
Main way is episomal replication in the nucleus
Alternative is what retroviruses do and integrate its genome into host chromosomes
Why do some viruses benefit from autophagy?
Protect against cell death
Maintains viral reservoir
Enhance virus production
Why do some viruses have to combat autophagy?
Sequesters virus particles
Promotes latency
What HCV protein inactivates RIG-I signalling?
HCV NS3
What is incorporated into virions to inactivate complement?
CD55/CD59
What does EBNA-1 do?
Prevents processing of viral proteins therefore stops activation of T cell response
What happens when herpes virus goes into latent stage?
No viral DNA or RNA produced, no activation of immune response, dont get activation of recognition
What is the virus in which we know there is a largest amount of genetic difference in a single host?
Hepatitis C virus, one species of virus, 40% difference in its nucleotide sequence
Why does hepatitis C have such a large genetic difference?
RNA-dependent RNA polymerase has no error checking
What happens when a cell is infected in lytic stage with herpesvirus?
That cell will be destroyed, this is what causes cold sores
Where do alphaherpes viruses establish latent infections?
In sensory neurones
What are beta gene expressions?
Polymerases and replication enzymes
When are LATs produced?
During replication, as long as virus has infected the right cell, it can go into latent stage and produce LATs
What are most LATs?
Intron sequences spliced from an 8.3kb transcript
What do LATs do?
Promote cell survival - (block Nfkappab, block apoptosis)
Inhibit AKT kinase, can switch off process associated with caspase 3 recruitment and activation - apoptosis
Where does EBV establish productive infection?
In the oropharyngeal mucosa
What type of virus is EBV?
Gammaherpesvirus
What type of cell does EBV establish latency within?
B cells
What does EBNA-1 do?
Required by the cell in latent states - expressed in all stages of latency
What does EBNA-1 bind to?
OriP
What are the two essential elements of OriP?
DS and FR
What is DS in OriP?
Contains 4 low affinity binding sites for EBNA-1 and is the origin of replication
What is FR in OriP?
Contains 20 copies of a 30bp sequence, each containing a high affinity site for EBNA-1
What inhibits EBNA-1 from being degraded?
Has a Gly-Gly-Ala repeat at its amino terminus
What is EBV latency I expression of?
EBNA-1 and LMP-2A only
What is latency II expression of?
EBNA-1, LMP-1 and LMP-2
Where is latency-I found?
In EBV-positive Burkitt’s lymphoma, NK-cell lymphoma and gastric cancer
Where is EBV latency II found?
Hodgkin’s disease and nasopharyngeal carcinoma
How many genes are expressed in latency III?
9 EBV genes
What are the chances of getting integration into transcripitonally active v non-active sites and why?
Into active sites is greater as it is rarely unwound
