Retrovirus Replication Flashcards
What are retroviruses?
Enveloped
ssRNA
7-12Kb
reverse transcription of viral genome into duplex
What is the structure of the retroviral particle?
Gag Pol Env 2 x ssRNA Lipid bilayer
What are some features of the retroviral genome
PBS 5' unique sequence Direct repeat sequence PPT 3' unique sequence
What is HIV-1 reverse transcriptase?
Heterodimer - p66, p51
RNaseH - degrades an RNA strand if its present in a RNA:DNA hybrid
Initiation of reverse transcription?
initiation follows the annealing a partially unwound tRNA to the 3’ end of PBS
What is the polypurinetract resistant to?
RNaseH - usually chews up RNA part of RNA:DNA hybrid
What is second strand transfer?
one end - plus-end PBS
other end - minus-end PBS
ds copy of DNA genome
affinity between + and - ends
What is provirus integration?
Preintegration complex (PIC) - contains proviral DNA, capsid & integrase
mediated by integrase - catalyses a series of independent events = cleavage of host DNA, splice provirus into the cleavage site
How does retrovirus transcription take place?
integrated provirus = functions as normal gene locus
5’LTR = enhancer/promoter
3’LTR = mediates polyadenylation of RNA transcripts
U3 recruits TFs - need replication of U3
What happens during retrovirus mRNA splicing?
splice sequences out
What are endogenous retroviruses?
present in all vertebrate species
infection of germ line cells
generally defective
What are HERVs?
human endogenous RetroViruses
designated by a single letter code for tRNA primer
8000 pol-containing proviral elements
germ line infections over millions of years
estimated time of insertion - evolution rate of 5x10-9 per year
What is the most recent HERV?
HERK-K113
What are the beneficial effect of HERVs?
Ability to digest starch - insertion of provirus upstream of duplicated copy of pancreatic amylase
Development of placenta - Synctins expressed, membrane fusion activity
What are detrimental effects of HERVs?
Associated with autoimmune diseases/cancer - type 1 diabetes
Behavioural effects - addictive behaviour
