WEEK 4: HIV AND AIDS Flashcards

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1
Q

what is a retrovirus?

A

a large and diverse family of enveloped RNA viruses. Virions are approx 80-120nm. Lipid envelope that’s derived from host cells membrane. Display retrovirus glycoproteins. RNA is 7-12k bases, non-segmented, single stranded, positive polarity (can get picked up by host ribosomes).

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2
Q

what’s a lentivirus?

A

group of retroviruses that cause immunodeficiency in any group they infect.

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3
Q

what is a simple retrovirus?

A

It has 3 genes: GAG/POLYMERASE (POL)/ENVELOPE. POL gene encodes 3 enzymes: reverse transcriptase (RT) that converts RNA to DNA, integrase (INT) enzyme integrates DNA into host genome, protease (PR) is essential for polypeptide processing.

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4
Q

what is a complex retrovirus?

A

Contains the same genes as simple but has accessory genes. These can down regulate the immune system in favour of the virus.

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5
Q

why are lentiviruses more complex than simple retroviruses?

A

their genome also encodes accessory proteins.

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6
Q

what 3 types of immune cells does HIV infect?

A

CD4+ T lymphocytes (Th)
macrophages
dendritic cells

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7
Q

what is AIDS caused by in the body?

A

profound susceptibility to opportunistic infections and cancers as a result of progressive depletion of CD4+ T cells.

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8
Q

how many people globally are HIV +?

A

0.8%

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9
Q

how many people develop AIDS from HIV 1 and HIV 2?

A

HIV 1 - 99.9%
HIV 2 - 20-25%

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10
Q

what is the difference between HIV 1 & 2?

A

HIV-2 encodes gag subunit p26 whereas HIV-1 encodes gag subunits p24

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11
Q

where did HIV originate?

A

In the Democratic republic of Congo, chimpanzees infected with SIV CPZ were hunted and eaten which causes HIV in humans.

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12
Q

What groups are at high risk of HIV?

A
  • men that have sex with men
  • black Africans
  • young people between 15-21
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13
Q

how many proteins does the RNA code for?

A

15 different proteins

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14
Q

how is HIV detected?

A

detection of serum antibodies to the envelope and GAGs. positive = exposure to virus.
then
genes are detected and viral load will be quantified. higher viral load equates to higher antiviral therapy.

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15
Q

How is the progression to AIDS monitored?

A

CD4+ T cell count. Monitor the ratio between CD4+/CD8+.

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16
Q

How can IgM and IgG assay indicate HIV infection?

A

More IgM and low IgG - recent infection. Vice versa - chronic infection.

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17
Q

What does the GAG gene encode for?

A

the matrix, the capsid and the nucleocapsid. Also the p6.

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18
Q

What does the POL gene encode for?

A

protease, reverse transcriptase, integrase.

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19
Q

What does the envelope gene encode for?

A

gp 120 and gp 41.

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20
Q

What are the 6 accessory proteins of HIV?

A

vif, vpr, vpu, tat, rev, nef

21
Q

What do the accessory proteins of HIV do?

A

They make the virus a better version so it can fulfil its replication cycle.

22
Q

how many bases is in HIV’s RNA genome?

A

9.8 kb (9800)

23
Q

what is the function of the long terminal repeats ?

A
  1. control transcription of the viral genome
  2. where they will integrate the genes into the host cell genome
  3. binding site for host transcription factors
24
Q

how many open reading frames does HIV have?

A
  1. They overlap slightly
25
Q

what 2 receptors does HIV require to enter a cell?

A

must bind to CD4 and a chemokine receptor

26
Q

what part of HIV virion binds to receptors on target cell?

A

via envelope glycoproteins

27
Q

what does a chemokine receptor do?

A

orchestrates the movement of immune cells. Moves cells to locations they are needed.

28
Q

What are the 2 chemokine receptors needed for HIV entry into target cell

A

CCR5 and CXCR4

29
Q

What chemokine coreceptor does R5-Tropic virus bind to to gain entry?

A

CCR5 receptor (and CD4)

30
Q

What chemokine coreceptor does Dual-Tropic virus bind to to gain entry?

A

EITHER CCR5 or CXCR4 (and CD4)

31
Q

What chemokine coreceptor does X4-Tropic virus bind to to gain entry?

A

CXCR4 (and CD4)

32
Q

What chemokine receptor is associated with the viraemic and latent phase?

A

CCR5

33
Q

What chemokine receptor is associated with the AIDS phase?

A

CXCR4

34
Q

What does a mutation of CCR5 do?

A

It prevents the expression of a functional CC receptor and consequently prevents viral binding, fusing and entry.

35
Q

What does reverse transcriptase do?

A

converts its RNA into viral DNA in a process called reverse transcription

36
Q

Why is HIV so hyper variable? 4 reasons

A
  1. 2 copies of RNA packaged per virion.
  2. RT lacks proof reading ability therefore mutations occur in 1 every 17000 bases.
  3. 10 billion viruses are produced everyday from infected cells.
  4. Half life is so short
37
Q

How is HIV transmitted?

A
  1. sexual route
  2. blood products (transfusion, drug users)
  3. mother to child in: utero, during labour or breast feeding. Breast feeding is most transmissible because CD4+ T cells line epithelium of the breast.
38
Q

first phase of HIV?

A
  • < 2 weeks.
  • HIV infection of first cells, CD4+ T cell
  • systemic spread via lymph nodes
  • interferon response
  • viral reservoir established
  • massive replication of HIV in the GALT (gut associated lymphoid tissue) and tissue destruction leading to enteropathy (damage to small intestine)
39
Q

second phase of HIV ?

A
  • between 2-4 weeks
  • high levels of viremia and it peaks
  • flu like symptoms
  • large numbers of activated CD4+ T cells - these cells are producing loads of HIV virions
  • transient decline in blood CD4 + T cells
40
Q

third phase of HIV?

A
  • chronic phase
  • viral “set point” is established
  • progressive loss of CD4 + T cells
  • chronic inflammation
  • immune cell exhaustion
  • progression to AIDS
41
Q

fourth phase of HIV?

A
  • between 1 and 20 years
  • CD4+ T cells per microlitre increases risk of infectious complications
  • <200 cells per microlitre increases risk of life threatening AIDS defining illnesses
42
Q

what are symptoms of chronic HIV?

A

dramatic weight loss, chronic diarrhoea, night sweats, skin problems, life threatening illnesses

43
Q

What 2 HLA (human leukocyte antigen) types are favourable to responding to HIV

A

HLA-B27 and HLA-B57

44
Q

how is HIV managed with drugs?

A

HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) (consists of 30 drugs)​. Triple drug therapy is also used as HIV can quickly adapt and become resistant

45
Q

How does HAART work?

A

It inhibits:
- receptor interactions
- activity of fusion
- activity of RT
- activity of integrase
- protease activity

46
Q

What stage of the activity cycle is HAART unable to inhibit?

A

the assembly inhibitors

47
Q

what is the most common nucleoside reverse transcriptase inhibitor(drug) mutation?

A

M184V. Methionine replaces valine at codon 184.

48
Q

What drugs do M184V show reduced susceptibility to?

A

Emtricitabine (FTC)​
&
Lamivudine (3TC)​

49
Q

What drugs do M184V show increased susceptibility to?

A

Tenofovir disoproxil fumarate (TDF)​
&
Didanosine (ddI)​
&
Zidovudine (AZT)