Virology of HIV Flashcards
(38 cards)
Why are HIV patients immunosuppressed?
Because of HIV infects and kills CD4 T cells.
What kinds of HIV are there? Which is more pathogenic?
HIV-1 and HIV-2
HIV-1 evolved from chimpanzees is more pathogenic
HIV-2 evolved from macaques is less pathogenic
How many AIDS related deaths per year?
1.6 million
What 6 things outside to in make up HIV?
envelope (from budding of host PM).
Envelope proteins (important for infections)
Matrix (important for mechanical properties)
capsid
nucleocapside (proteins associated with the RNA)
RNA genome
How many RNA molecules within a HIV capsid?
2 RNA genomes associated with nucleocapsid proteins.
2 examples of nucleocapsid proteins
Reverse transcriptase and Integrase (integrates viral DNA into host chromosome).
What are the two envelope proteins and what is their localisation?
gp120 (extracellular) gp41 (transmembrane).
How large is a normal human gene vs the HIV genome?
Normal human gene can be 5-30kb.
HIV genome is 10kb and contains 15 genes.
How does HIV genome compact genes?
Uses polyproteins, and different open reading frames.
Also uses alternative splicing.
What three polyproteins are produced, and which is produced in highest amount.
GAG, POL and ENV.
GAG ORF is transcribed 90% of the time.
Frameshifts generate other ORFs.
What 6 proteins come from the GAG and POL polyproteins?
GAG: Matrix, capsid and nucleocapsid
POL: protease, reverse transcriptase and integrase
What is the ENV polyprotein called and what do its cleavage products in the ER produce?
gp16, cleaved into gp120 and gp41.
What post-translational modification makes GAG polyprotein anchored to pM?
palmitoylation.
What happens when budded off immature virion matures?
Protease activity cleaves to form matrix and capsid containing nucleocapsid and RNA genomes.
Why does HIV’s use of splicing mean there’s pressure for codon maintenance?
Because 3 different proteins spliced from same area, need to preserve nucleotides here or could risk negatively affecting 1 or more of the proteins.
Describe the process of Cell infection?
gp120 interacts with CD4, and with CCR5/CXCR4 via loop.
This brings envelope and PM into close contact and gp41 can embed in PM.
Drives conformational changes that allow PM to come close enough to fuse together.
How does CCR5/ CXCR4 affect HIV tropism and disease progression?
CCR5 tropic HIV cells will infect macrophages more preferentially, slower progression.
CXCR4 will infect CD4 T cells more readily causing more aggressive progression to AIDS.
What molecule is initiation of reverse transcription of the HIV genome dependant on?
tRNA specific to lysine.
Where does tRNA specific to lysine bind?
hybridises at pbs gene region, initaiton reverse transcriptino of R U5 region.
What happens after R U5 cDNA hybridises to the R sequence?
The rest of the RNA molecules is reversed transcribed and degraded (through RNAase H activity) except for ppt.
ppt hybridizes and initiates reverse transcription in the opposite direction so that the pbs ‘primer’ is converted to cDNA. Complementary pbs portions can hybridize and the rest of the genome converted to ds cDNA.
What molecules would stop reverse transcription of ‘free’ HIV RNA?
APOBEC3G and SAMHD1.
How would APOBEC3G and SAMHD1 and block free HIV genomes?
APOBEC3G would interfere with transcription and SAMHD1 would eliminate dNTPs required for reverse transcription.
What does TRIM5 do?
causes premature disassembly of HIV capsid.
What early phased proteins are translated first?
double spliced mRNA like rev, nef vpu, vif, vpr and tat.
