HIV Pathogenesis Flashcards
what were AIDS first documented cases?
early 80s
- young men with serious lung infection caused by fungues
- young men with new cancer with neck, back, and mounth lesions
AIDS transmission modes? rate of transmission?
- sexual interaction
- birth
- needles intravenous
- blood transfusions at birth
difficult to transmit: 1/1000 chance
what is antiretroviral therapy for AIDS?
cART (combined Antiretroviral therapy) - cocktail daily
family, subfamily, and subtypes of viruses of HIV?
fam: retroviridae
subfamily: lentiviruses
subtypes: HIV-1, HIV-2
what is a structural characteristic of HIV?
has envelope
replication process of HIV?
- HIV +ssRNA + viral RNA dependent DNA polymerase (reverse transcriptase) makes ssDNA
- ssDNA + DNA poly (or rev. transc.) makes ss/ds DNA then dsDNA
- dsDNA + DNA dependent RNA poly makes +ssRNA -> proteins
integrated forever!
what are the important proteins and their glycoproteins?
- Surface protein: gp120: viral receptor
- Transmembrane protein: gp4: fusion protein
- Capsid protein: p24
1 and 2 are on exterior envelope
3 is outside core within the virus
What is PIC?
Pre-Integration Complex – Will be transcribed to produce +mRNA after HIV-1 core enters nucleus and capsid is uncoated
what are the characteristics of reverse transcriptase?
- polymerase that lack’s 3’-5’ exonuclease proofreading activity making 1-10 nucleotide errors/synthesis
- makes a diverse collection of variants called QUASISPECIES
3 important sequences on retrovirus genome?
Gag: structural proteins: capsid, matrix protein, nuclear capsid
Pol: enzymatic activity: reverse transcriptase, integrase, protease
Env: envelope: gp120 and gp41
What is proviral DNA?
viral DNA integrated into host genome at random site by integrase (inside core of HIV)
how does integrase at proviral DNA into host?
- removes 2 3’ terminal nucleotides on each strand
- viral DNA inserted by free 3’OH ends ligated into cleaved segment of host genome
Where did HIV/AIDS originate from? How was this determined?
- central Africa in 1959 in Zaire and Rwanda sex workers
- found from sequencing
What are the subgroups of HIV?
HIV-1 (Groups M, N, O, P) - also subgroups to M
HIV-2
M,N,O and P represents a transfer from an animal to a human
What are some subtypes of HIV-1-M and their characteristics?
C: most prevalent
B: north america
D: quick death
CRFs: sex workers infected many types
what are CRFs?
circulating recombinant
forms: mixtures of
various subtypes
- more virulent
How does HIV-2 compare to HIV-1?
HIV-2 does not progress to AIDS as quickly, not as transmissible, not as deadly
What is HIV-1 similar to>
other lentivirus called SIV that came from chimpanzees
How was HIV-1 sourced to be similar to SIV?
- Virus measured in fecal
samples of chimp populations - Chimps don’t swim = isolate populations by water
- Pan troglodytes schweinfurthii and
Pan troglodytes troglodytes have SIV but the latter matches HIV-1 sequence
How did the zoonotic event of SIV to HIV occur?
old world monkeys have virus but it is non pathogenic to them
chimps must have eaten old world moneys and got SIV
SIV transmitted to humans through bushmeat hunting (group M)
how did HIV turn into an outbreak? What did it need?
accelerators: European colonization : urban centres, sex workers
Introduction of health care to African population
Why is HIV-1 transmission difficult?
HIV-1 is pretty whimpy: 10% bleach, heat ,
air drying or pH variance will inactivate it – but these are not present during transmission