HIV Pathogenesis

Question 1

what were AIDS first documented cases?

Answer 1

early 80s
- young men with serious lung infection caused by fungues
- young men with new cancer with neck, back, and mounth lesions

Question 2

AIDS transmission modes? rate of transmission?

Answer 2

• sexual interaction
• birth
• needles intravenous
• blood transfusions at birth

difficult to transmit: 1/1000 chance

Question 3

what is antiretroviral therapy for AIDS?

Answer 3

cART (combined Antiretroviral therapy) - cocktail daily

Question 4

family, subfamily, and subtypes of viruses of HIV?

Answer 4

fam: retroviridae
subfamily: lentiviruses
subtypes: HIV-1, HIV-2

Question 5

what is a structural characteristic of HIV?

Answer 5

has envelope

Question 6

replication process of HIV?

Answer 6

1. HIV +ssRNA + viral RNA dependent DNA polymerase (reverse transcriptase) makes ssDNA
2. ssDNA + DNA poly (or rev. transc.) makes ss/ds DNA then dsDNA
3. dsDNA + DNA dependent RNA poly makes +ssRNA -> proteins

integrated forever!

Question 7

what are the important proteins and their glycoproteins?

Answer 7

1. Surface protein: gp120: viral receptor
2. Transmembrane protein: gp4: fusion protein
3. Capsid protein: p24

1 and 2 are on exterior envelope
3 is outside core within the virus

Question 8

What is PIC?

Answer 8

Pre-Integration Complex – Will be transcribed to produce +mRNA after HIV-1 core enters nucleus and capsid is uncoated

Question 9

what are the characteristics of reverse transcriptase?

Answer 9

• polymerase that lack’s 3’-5’ exonuclease proofreading activity making 1-10 nucleotide errors/synthesis
• makes a diverse collection of variants called QUASISPECIES

Question 10

3 important sequences on retrovirus genome?

Answer 10

Gag: structural proteins: capsid, matrix protein, nuclear capsid

Pol: enzymatic activity: reverse transcriptase, integrase, protease

Env: envelope: gp120 and gp41

Question 11

What is proviral DNA?

Answer 11

viral DNA integrated into host genome at random site by integrase (inside core of HIV)

Question 12

how does integrase at proviral DNA into host?

Answer 12

1. removes 2 3’ terminal nucleotides on each strand
2. viral DNA inserted by free 3’OH ends ligated into cleaved segment of host genome

Question 13

Where did HIV/AIDS originate from? How was this determined?

Answer 13

• central Africa in 1959 in Zaire and Rwanda sex workers
• found from sequencing

Question 14

What are the subgroups of HIV?

Answer 14

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

Question 15

What are some subtypes of HIV-1-M and their characteristics?

Answer 15

C: most prevalent
B: north america
D: quick death
CRFs: sex workers infected many types

Question 16

what are CRFs?

Answer 16

circulating recombinant
forms: mixtures of
various subtypes
- more virulent

Question 17

How does HIV-2 compare to HIV-1?

Answer 17

HIV-2 does not progress to AIDS as quickly, not as transmissible, not as deadly

Question 18

What is HIV-1 similar to>

Answer 18

other lentivirus called SIV that came from chimpanzees

Question 19

How was HIV-1 sourced to be similar to SIV?

Answer 19

1. Virus measured in fecal
   samples of chimp populations
2. Chimps don’t swim = isolate populations by water
3. Pan troglodytes schweinfurthii and
   Pan troglodytes troglodytes have SIV but the latter matches HIV-1 sequence

Question 20

How did the zoonotic event of SIV to HIV occur?

Answer 20

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)

Question 21

how did HIV turn into an outbreak? What did it need?

Answer 21

accelerators: European colonization : urban centres, sex workers
Introduction of health care to African population

Question 22

Why is HIV-1 transmission difficult?

Answer 22

HIV-1 is pretty whimpy: 10% bleach, heat ,
air drying or pH variance will inactivate it – but these are not present during transmission