L68

Question 1

What is the family & genus of HIV?

Answer 1

Family = retrovirus (RNA –> DNA)

Genus - lentivirus (long incubation time)

Question 2

What does a high error rate of reverse transcriptase yield?

Answer 2

HIV evolution –> drug resistance

Question 3

What are the 2 important proteins of the HIV envelope?

Answer 3

Gp120 + gp41 = spike

Coded from env

Question 4

What is gag p17?

Answer 4

Matrix

Lines inner leaflet of envelope

Question 5

What is gag p24?

Answer 5

The capsid that encloses HIV RNA + enzymes + proteins

Question 6

Which enzymes are carried with HIV in active form?

Answer 6

= regulatory proteins

1. Reverse transcriptase - to code DNA once inside host cell
2. Integrase - follows RT
3. Protease - was used to mature the virion after budding

Question 7

What is the diagnostic marker used to measure the effectiveness of anti-retroviral therapies?

Answer 7

HIV RNA 
gag p24 (capsid)

Question 8

What part of HIV is the therapeutic target?

Answer 8

The enzymes!

Kill these - make the virus ineffective

Question 9

What are modes of HIV transmission?

Answer 9

Sex
During birth
Needles! IVDUs

Question 10

How does HIV get into tissues?

Answer 10

1. Break mucosal epi barrier
2. Transcytosis
   Either way = bad b/c 1st responder likely to be CD4 = infection target

Question 11

How does HIV attach to host cells?

Answer 11

Gp41/120 spike + CD4

Conformational change –> membranes together

Question 12

What is required for HIV-host membrane fusion?

Answer 12

Co-receptor binding (by different part of gp120)
CCR5 and/or CXCR4
- Found on macrophages & T cells (cell trophism)
MEANS that entry requires TRIMER formation: gp41/120 + CD4 + co-receptor

Question 13

What is the pre-integration complex vs provirus?

Answer 13

Pre-integration complex = how enters nucleus w/ integrase

Provirus = after in host DNA

Question 14

How can genetics or drugs affect HIV by working at CCR5?

Answer 14

Genetics:
- Mutated –> no CCR5 fxn but also no HIV co-receptor needed for binding
Drug target - Maraviroc

Question 15

What are the 3 types of RT inhibitors?

Answer 15

Nucleoside analogs
NucleoTIDE analogs
Non-nucleoside analogs
All 3 change RT’s fxn = X RNA –> DNA

Question 16

What are HIV long terminal repeats (LTRs)?

Answer 16

Identical RNA on both ends (5 & 3’) of the genome

Used for integration

Question 17

Where do transcription factors that regulate expression of viral genes bind?

Answer 17

@ 5’ LTR

Question 18

What are the 3 classes of RNA molecules produced during viral replication? Which are packaged into the virus?

Answer 18

2kb, 4kb - 9kb into new virus

Question 19

Which RNA protein is used to make the initial HIV diagnosis?

Answer 19

gag p24

Question 20

What are the 3 structural genes on the RNA genome?

Answer 20

Gag (non-envelope membranes)
Pol (polymerases)
Env (envelope)

Question 21

What 2 proteins are coded for by the gag gene?

Answer 21

gag p24 = capsid

gag p17 = matrix, lines inner leaflet of viral envelope

Question 22

What 3 proteins are coded for by the pol gene?

Answer 22

RT
Integrase
Protease

Question 23

What 3 proteins are coded for by the env gene?

Answer 23

gp 120 & 41

Question 24

What are the 2 regulatory genes of the HIV genome?

Answer 24

Tat - needed for initiation & elongation starting at 5’ LTR
Rev - transports new virion RNA into the cytoplasm

Question 25

What are the 4 accessory proteins/genes on the HIV genome?

Answer 25

``` nef vpr vpu vif As a group, remove restriction factors that host cell uses to stop DNA replication when senses infection ```

Question 26

Which cells can HIV target to change function and create immune deficiency?

Answer 26

``` CD 4 & CD8 T cells B cells Myeloid DCs Plasmacytoid DCs Uninfected bystander cells ```

Question 27

What is pyroptosis?

Answer 27

HIV induced cell death that is VERY inflammatory | Recruits other immune cells --> prime for infection

Question 28

What is the viral load?

Answer 28

In acute infection, when virus in plasma peaks

Question 29

What is the viral set point?

Answer 29

When CD8 response rises to control viral replication | - Allows recruitment of Ab response

Question 30

How can HIV infected cells kill uninfected bystanders?

Answer 30

Infected - normal CD95L - CD95 gp41/120 - CD4/CXCR4 death signals

Question 31

Which 2 cytokines have anti-HIV properties?

Answer 31

IL10 | IFNg

Question 32

Which HLA subtypes have natural protection against HIV?

Answer 32

B 27 & 57

Question 33

Describe the T cell HIV vaccine.

Answer 33

Infect APCs to present HIV to T cells --> create stronger immune response if the virus actually presents Problem = Too late, could have already est infection in APCs More therapeutic

Question 34

Describe the B cell HIV vaccine?

Answer 34

Abs vs gp 41/120 - no initial binding & prevent 1ary infection Problem: HIV variation & getting Abs that are long lasting in high [ ]s

Question 35

What are the 2 major HIV vaccine trials?

Answer 35

STEP = T cell vaccine, failure, increased infection | RV144 Thai = B cell vaccine, saw 31% less infection