WEEK 4: HIV AND AIDS

Question 1

what is a retrovirus?

Answer 1

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).

Question 2

what’s a lentivirus?

Answer 2

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

Question 3

what is a simple retrovirus?

Answer 3

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.

Question 4

what is a complex retrovirus?

Answer 4

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

Question 5

why are lentiviruses more complex than simple retroviruses?

Answer 5

their genome also encodes accessory proteins.

Question 6

what 3 types of immune cells does HIV infect?

Answer 6

CD4+ T lymphocytes (Th)
macrophages
dendritic cells

Question 7

what is AIDS caused by in the body?

Answer 7

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

Question 8

how many people globally are HIV +?

Answer 8

0.8%

Question 9

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

Answer 9

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

Question 10

what is the difference between HIV 1 & 2?

Answer 10

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

Question 11

where did HIV originate?

Answer 11

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

Question 12

What groups are at high risk of HIV?

Answer 12

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

Question 13

how many proteins does the RNA code for?

Answer 13

15 different proteins

Question 14

how is HIV detected?

Answer 14

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.

Question 15

How is the progression to AIDS monitored?

Answer 15

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

Question 16

How can IgM and IgG assay indicate HIV infection?

Answer 16

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

Question 17

What does the GAG gene encode for?

Answer 17

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

Question 18

What does the POL gene encode for?

Answer 18

protease, reverse transcriptase, integrase.

Question 19

What does the envelope gene encode for?

Answer 19

gp 120 and gp 41.

Question 20

What are the 6 accessory proteins of HIV?

Answer 20

vif, vpr, vpu, tat, rev, nef

Question 21

What do the accessory proteins of HIV do?

Answer 21

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

Question 22

how many bases is in HIV’s RNA genome?

Answer 22

9.8 kb (9800)

Question 23

what is the function of the long terminal repeats ?

Answer 23

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

Question 24

how many open reading frames does HIV have?

Answer 24

9. They overlap slightly

Question 25

what 2 receptors does HIV require to enter a cell?

Answer 25

must bind to CD4 and a chemokine receptor

Question 26

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

Answer 26

via envelope glycoproteins

Question 27

what does a chemokine receptor do?

Answer 27

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

Question 28

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

Answer 28

CCR5 and CXCR4

Question 29

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

Answer 29

CCR5 receptor (and CD4)

Question 30

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

Answer 30

EITHER CCR5 or CXCR4 (and CD4)

Question 31

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

Answer 31

CXCR4 (and CD4)

Question 32

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

Answer 32

CCR5

Question 33

What chemokine receptor is associated with the AIDS phase?

Answer 33

CXCR4

Question 34

What does a mutation of CCR5 do?

Answer 34

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

Question 35

What does reverse transcriptase do?

Answer 35

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

Question 36

Why is HIV so hyper variable? 4 reasons

Answer 36

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

Question 37

How is HIV transmitted?

Answer 37

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.

Question 38

first phase of HIV?

Answer 38

- < 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)

Question 39

second phase of HIV ?

Answer 39

- 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

Question 40

third phase of HIV?

Answer 40

- chronic phase - viral "set point" is established - progressive loss of CD4 + T cells - chronic inflammation - immune cell exhaustion - progression to AIDS

Question 41

fourth phase of HIV?

Answer 41

- 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

Question 42

what are symptoms of chronic HIV?

Answer 42

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

Question 43

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

Answer 43

HLA-B27 and HLA-B57

Question 44

how is HIV managed with drugs?

Answer 44

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

Question 45

How does HAART work?

Answer 45

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

Question 46

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

Answer 46

the assembly inhibitors

Question 47

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

Answer 47

M184V. Methionine replaces valine at codon 184.

Question 48

What drugs do M184V show reduced susceptibility to?

Answer 48

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

Question 49

What drugs do M184V show increased susceptibility to?

Answer 49

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