Retroviruses Flashcards
Retrovirus RNA structure
Dimeric ssRNA
Retrovirus genes
LTR - PBS + packaging signal - gag - pol - env - polypurine tract -LTR
Retrovirus life cycle
Fusion
core released into cytoplasm
RT reaction in cytoplasm
dsDNA goes to nucleus and integrated into host genome
Function of LTRs
contain regulatory elements for gene expression
Morphology and taxonomy of retroviruses
Enveloped viruses with surface spikes
spherical w diameter of 80-100nm
core is spherical or rod-shaped
Origin of retroviruses
evolved from simpler RT elements
Retrovirus general structure
Transmembrane + surface glycoproteins
Lipid envelope
Matrix proteins
Capsid proteins
Attached to RNA: Nucleocapsid proteins, RT, Integrase
What does env encode?
Transmembrane and surface glycoproteins
Variable regions
Retrovirus entry
SU binds to receptor
Causes conformational change in TM trimer
Fusion peptide activated and facilitates membrane fusion
Only viral core enters
Common retroviral targets
Usually immune cells e.g. macrocytes - main reservoir
Where does Reverse transcription occur
cytoplasm in virion core
Steps of RT
7 steps
In what direction does Rt synthesise DNA
3’-5’ direction
What is the R region in retrovirus genome
LTR containing promoter and primer binding sites
encodes a polyadenylase
Polypyrimidine tract
Acts as primer for second strand synthesis - immune to RNAseH activity
The purpose of the polypyrimidine tract in the retroviral genome is to act as a splicing signal for the viral RNA.
Retrovirus integration
Controlled by Integrase (pol)
Makes staggered cuts
Only integrates in activitely transcribing areas of genome - can only fit here
What do retroviruses use to regulate gene expression?
Motifs that bind transcription factors
Promoter and enhancer motifs
HIV gene expression regulators
Tat and TAR
Tat
Transactivator
Accessory protein that binds to TAR
Mediates phosphorylation of host polymerase to fully elongate RNA
TAR
Region of viral mRNA which Tat binds to
rev
controls export of RNA especially structural genes from nucleus
nuclear localisation signal
How is complete splicing prevented in the nucleus?
- Inefficient splicing w bad splicing
- RNA secondary structure that bind to host proteins + help export
- Viral protein produced e.g. HIV/ATLV rev
How does rev work in HIV
early stages: rev produced by splicing, there’s none atm
RNA gets spliced - accesory proteins prodcued and no structural produced
rev produced and enters nucleus + binds to rre in RNA -> promotes export
RRE
Rev Responsive Element
Looped secondary structure in HIV ssRNA
How is Pol produced?
Translated as part of gag/pol polyprotein
20:1 gag:pol ratio –> need many more copies of gag
Termination suppression
Looped secondary structure after UAG stop codon
1 out of 20 times it causes ribosome to misread the codon
Pol produced w gag
Gammaretroviruses
Ribosomal frameshifting
The HIV genome contains a frameshift signal/slippery sequence in the gag-pol region, which directs the ribosome to shift the reading frame from the gag gene to the pol gene during translation. This results in the production of a Gag-Pol fusion protein, which is then cleaved into individual Gag and Pol proteins by the viral protease.
Where is env processed
ER and golgi
Particle formation
