L68 Flashcards

1
Q

What is the family & genus of HIV?

A

Family = retrovirus (RNA –> DNA)

Genus - lentivirus (long incubation time)

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2
Q

What does a high error rate of reverse transcriptase yield?

A

HIV evolution –> drug resistance

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3
Q

What are the 2 important proteins of the HIV envelope?

A

Gp120 + gp41 = spike

Coded from env

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4
Q

What is gag p17?

A

Matrix

Lines inner leaflet of envelope

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5
Q

What is gag p24?

A

The capsid that encloses HIV RNA + enzymes + proteins

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6
Q

Which enzymes are carried with HIV in active form?

A

= 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
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7
Q

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

A
HIV RNA 
gag p24 (capsid)
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8
Q

What part of HIV is the therapeutic target?

A

The enzymes!

Kill these - make the virus ineffective

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9
Q

What are modes of HIV transmission?

A

Sex
During birth
Needles! IVDUs

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10
Q

How does HIV get into tissues?

A
  1. Break mucosal epi barrier
  2. Transcytosis
    Either way = bad b/c 1st responder likely to be CD4 = infection target
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11
Q

How does HIV attach to host cells?

A

Gp41/120 spike + CD4

Conformational change –> membranes together

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12
Q

What is required for HIV-host membrane fusion?

A

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

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13
Q

What is the pre-integration complex vs provirus?

A

Pre-integration complex = how enters nucleus w/ integrase

Provirus = after in host DNA

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14
Q

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

A

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

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15
Q

What are the 3 types of RT inhibitors?

A

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

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16
Q

What are HIV long terminal repeats (LTRs)?

A

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

Used for integration

17
Q

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

A

@ 5’ LTR

18
Q

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

A

2kb, 4kb - 9kb into new virus

19
Q

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

A

gag p24

20
Q

What are the 3 structural genes on the RNA genome?

A

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

21
Q

What 2 proteins are coded for by the gag gene?

A

gag p24 = capsid

gag p17 = matrix, lines inner leaflet of viral envelope

22
Q

What 3 proteins are coded for by the pol gene?

A

RT
Integrase
Protease

23
Q

What 3 proteins are coded for by the env gene?

A

gp 120 & 41

24
Q

What are the 2 regulatory genes of the HIV genome?

A

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

25
Q

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

A
nef
vpr
vpu
vif 
As a group, remove restriction factors that host cell uses to stop DNA replication when senses infection
26
Q

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

A
CD 4 & CD8 T cells
B cells
Myeloid DCs
Plasmacytoid DCs
Uninfected bystander cells
27
Q

What is pyroptosis?

A

HIV induced cell death that is VERY inflammatory

Recruits other immune cells –> prime for infection

28
Q

What is the viral load?

A

In acute infection, when virus in plasma peaks

29
Q

What is the viral set point?

A

When CD8 response rises to control viral replication

- Allows recruitment of Ab response

30
Q

How can HIV infected cells kill uninfected bystanders?

A

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

31
Q

Which 2 cytokines have anti-HIV properties?

A

IL10

IFNg

32
Q

Which HLA subtypes have natural protection against HIV?

A

B 27 & 57

33
Q

Describe the T cell HIV vaccine.

A

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

34
Q

Describe the B cell HIV vaccine?

A

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

35
Q

What are the 2 major HIV vaccine trials?

A

STEP = T cell vaccine, failure, increased infection

RV144 Thai = B cell vaccine, saw 31% less infection