HIV (Dr. Cochrane) Flashcards

(56 cards)

1
Q

Origin of HIV?

A

from SIVcpz of chimpanzees

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2
Q

What happens when old world monkeys have HIV-1?

A

High level of viremia
BUT not immune deficiency

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3
Q

Differences between SIV infection in human in natural host

A

I) Level of peripheral CD4+ T cells:
Healthy in host, low in humans
II) immune dysfunction: only found in human
III) chronic immune activation: only in human

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4
Q

Factors affecting transmission efficiency

A

I) inflammation due to other infections increase number of target cells in mucus, mucosal envrionment
II) viral load in inoculum

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5
Q

Types of HIV-1

A

R5, X4

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6
Q

Which form can transmit acroos mucosal membrane?

A

R5

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7
Q

Site of SIV-1 replication?

A

Gastrointestinal tract
Nasal cavity
Male genital tract
Lymph nodes
Lungs

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8
Q

Cells infected by HIV-1

A

I) CD4+ T cells
II) Monocytes/macrophages

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9
Q

What happens after CD4+ T cell infected by HIV-1?

A

Infected cells can induce death of neigbouring T cells by pyroptosis due to abortve infection

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10
Q

What happens after macrophages are infected by HIV-1?

A

Can enhance HIV-1 infection of surrounding cells

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11
Q

what decides the progression of HIV infection/

A

Viral load setpoint
—> the higher, the quicker it reaches end pt

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12
Q

Why current treatments unable to cure HIV-1

A

I) residual levels of viral replication (not fully suppressed)
II) small pool of cells with silent integrated genomes persist
III) persistent immune dysfunctions

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13
Q

What co-receptor do X4 bind for entry?

A

CXCR4

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14
Q

What co-receptor does R5 bind to?

A

CCR5

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15
Q

How does HIV-1 enter our cells?

A

I) bind to CD4 —> change in gp120 on virus
II) change in gp120 allow binding to secondary receptor (CXCR4/CCR5)

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16
Q

A genetic mutation that led to HIV-1 resistance

A

Lacking CCR5

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17
Q

What happens during clinical latency that complicates cure?

A

Lots of new virions formed per day (2 billion)—> kill equal number of T cells
—> lots of new mutation arise, huge variety in HIV-1

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18
Q

What is HIV-1/2 transcription dependent on?

A

Activation state of cell (must be activated)

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19
Q

Why is HIV-1 most active in T cells?

A

Active NFAT, NFkappaB, AP2 present only in activated T cells

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20
Q

How does HIV-1 exploit adaptive immune system?

A

Once T cells activated, HIV-1 can infect it
—> can integrate into memory T cells
—> oncre reactivated —> able to expand and replicate new virions

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21
Q

How does viral insertion into cell DNA + long living infected cells affect treatment?

A

I) no idea where the reservoir is + reservoir established 3 days after exposure
II) take long time for treatment as those with silent virus are not killed thru drugs (take 60 years)
III) withdrawal of drugs —> infection reappear rlly quick

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22
Q

Approaches suggested to kill HIV

A

I) Shock and kill
II) enhance function of immune system
III) Scorched earth
IV) Block and lockH

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23
Q

How does shock and kill work?

A

Use agents to force cells to express latent virus —> immune system can detect and kill

24
Q

How does scorched earth work?

A

Wipe out all immune cells and replace with new ones resistant to virus

25
How does block and lock work?
Treat cells to prevent virus re-activation
26
Features in HIV-1 RNA
I) encodes for 9 proteins II) lots of splice donor (4) and acceptor sites (9)
27
HIV non strucutral genes crucial in cells
Tat, Rev
28
HIV non structural genes that are not essential in vitro (Needed for replication within host)
Nef, Vif, Vpr, Vpu
29
Common features of HIV-1 non structural genes
I) lack enzymatic function II) mediate new interactions between cellular factor
30
What is the function of Tat?
Increase viral RNA synthesis by increasing elongation efficiency of RNA Pol II
31
How does Tat increase RNA pol II’s elongation efficiency?
Bind to TAR at 5’ end of transcript —> recruit Cdk9, cyclin T to phosphoryltae C term of RNApol2
32
What is recruited after Tat binds to TAR on 5’ end?
Cdk9, cyclin T
33
What genes are early expressed in HIV-1?
Tat, Rev, Nef
34
Why are other genes expressed later?
Need Rev to induce export of incompletely spliced RNA
35
Role of non structural genes in HIV-1 that is not essential in vitro
I) allow HIV-1 to overcome innate defenses of host cell II) limit function of factors needed for adaptive immune response (MHC-I, II) + alter cell state to increase HIV-1 replication
36
What happens when HIV/SIV cannot express nef?
No or slow progression to AIDS
37
Function of Nef
I) remove CD4/MHC1 or II from cell surface II) Arrest of apoptosis in infected cells III) modulate T cell signalling IV) enhance viral infection
38
How does Nef remove CD4, MHCI or II from cell surface?
bridge CD4 with AP2, MHC with AP1 —> alter trafficking —> removed from cell surface
39
How does Nef enhance viral infection
Reduce surface expression of SERINC3, SERINC5
40
What happens to HIV lacking Vif?
- Reduced capacity to infect new cells - high levels of ApoBEC3F/G
41
Function of Vif
Increase infectivity of HIV-1 by inhibiting APOBEC
42
When does Vif act to help HIV-1?
During assembly of virus
43
What is APOBEC3F/G?
cytidine deaminases
44
What is the function of APOBEC3F/G?
selectively modify ssDNA
45
How does APOBEC3G perform its function?
induce hypermutation in viral genome
46
Function of Vpu?
I) Facilitate Gp120 release II) enhance virus release from cell surface
47
How does Vpu facilitate Gp120 release?
Induce degradation of CD4 in ER lumen
48
How does Vpu promote virus release?
Stimulate uptake of tetherin into endosome —> reduce expression of tetherin on membrane —> less HIV-1 accumulated in vesicles
49
Barriers to HIV-1 treatment and eradication
I) patient compliance (Need to maintain treatment) II) drug resistance III) viral latency (established early in infection + rebound is common after withdrawal from treatment)
50
Which types of infected cells have long life span
T helper memory cells (hv latent virus)
51
Which protein increase infectivity of HIV-1?
Vif-1
52
Which protein degrades host CD4?
Vpu
53
Which protein help with HIV-1 pathogenesis?
nef
54
function of Vpr
cell cycle arrest, induce cell death
55
Which protein is essential for expression of viral structural proteins?
Rev
56
Which protein increase viral RNA synthesis?
Tat