HIV and AIDS

Question 1

What is HIV?

Answer 1

Human Immunodeficiency Virus

Question 2

How many people are infected with HIV?

Answer 2

30-80 million people infected

Question 3

What does HIV cause?

Answer 3

AIDS

Question 4

What is AIDS?

Answer 4

Acquired Immuno Deficiency Syndrome

Question 5

Where did HIV begin?

Answer 5

In 1981 in Los Angeles- cluster of unusual cases of Kaposi’s sarcoma
Approx 100yrs ago SIV infected humans, species jump: SIV in non human primates in Sub-Saharan Africa

Question 6

What does HIV do?

Answer 6

Depletion of CD4+ T helper cells over 2-10 years

Question 7

What does HIV lead to?

Answer 7

Opportunistic infections
E.g. recurrent pneumonia, bacterial & viral
Direct effect of virus (wasting syndrome, neurological)

Question 8

What happens if a patient is left untreated with HIV?

Answer 8

Dies of diseases within 10 years

Question 9

What happens in HIV in the first week of infection?

Answer 9

HIV replication

Question 10

What happens during HIV within the first 6 weeks?

Answer 10

CD4+ cells depleted

Question 11

What then occurs after 6 week in HIV?

Answer 11

Gradual increase in virus copy number after that

Gradual decrease in CD4 cells of immune system

Question 12

What is HIV’s origins?

Answer 12

Central Africa roughly 100 years ago

Question 13

What is HIV closely related to?

Answer 13

SIV from chimpanzees, gorillas and SMs (mild disease)

Question 14

How was many of the original HIV cases obtained?

Answer 14

From eating or butchery

Question 15

How many types of HIV are there?

Answer 15

HIV-1 (main) and HIV-2 (niche in sub-saharan Africa) exist and share approx. 40% similarity

Question 16

What is HIV-1?

Answer 16

A diverse range of genotypes exist for HIV-1
These are based on sequence of variation and are divided in phylogenetic groups called M,N,O & P (2 people only)
O & P Gorillas

Question 17

What is the most common type of HIV-1 in the UK?

Answer 17

Clade B

Question 18

Where do most AIDS cases arise?

Answer 18

Developing countries (ART in the developed countries)

Question 19

How many people are infected with AIDS?

Answer 19

60 million globally

Question 20

How many people have died from AIDS in the last 30 years?

Answer 20

39 million

Question 21

What is the difference between HIV-1 and HIV-2?

Answer 21

HIV-1 is responsible for > 99% of AIDS cases in the west

HIV-2 is less virulent

Question 22

What do both HIV-1 and HIV-2 lead to?

Answer 22

AIDS (1>2)

Question 23

How is HIV and AIDS transmitted?

Answer 23

Sexually, M-B blood-borne (parenterally)

Question 24

What does HIV and AIDS lead to?

Answer 24

Chronic, persistent infection

Question 25

How long can HIV/AIDS patients be symptomless?

Answer 25

10 years

Question 26

What is the incidence of HIV-1 and AIDS?

Answer 26

Highest in sub-Saharan Africa Increasing in Eastern Europe and parts of Asia In areas of South Africa- infection rates of over 30% of the adult population of child bearing age

Question 27

What type of virus is HIV?

Answer 27

retrovirus

Question 28

What are the retroviridae family?

Answer 28

Enveloped, circular viruses 80-100nm in diameter Diploid positive sense RNA genome (7-12 kb), single stranded Replication strategy: reverse transcription (hence retro) to generate double stranded DNA followed by integration into host genome

Question 29

What is the HIV genome?

Answer 29

Complex gene organisation (9 in total) Encodes gag, pol, env (1-3) genes flanked by regulatory sequences called Long terminal repeats (LTRs) HIV has an additional 6 (4-9) accessory genes= rev, tat, nef, vif, vpr & vpu

Question 30

What are the 3 mains ORFS (within genome HIV-1)?

Answer 30

Gag- capsid, nucleocaspid, matrix (pro protease required for processing gag) Pol- reverse transcriptase, RNase H and integrase Env- envelope glycoproteins (SU (gpl120) & TM (gp41))

Question 31

What are the two regulatory genes in LTR?

Answer 31

Tat- transcriptional regulation; binds TAR in LTR | Rev- Regulates viral mRNA production and nuclear export

Question 32

What are the four accessory genes in LTR?

Answer 32

Nef- Regulates viral replication, interferes with host MHC class I and the CD4 receptor, affects T-cell activation, enhances infectivity Vif- Increases virion infectivity, affects virion assembly and/or cDNA synthesis Vpr- causes G2 arrest, facilitates nuclear entry of preintegration complex Vpu- affects virus release, disrupts env-CD4 complexes, degrades CD4

Question 33

For HIV what do glycoproteins gp120+ gp41 (ENV) form?

Answer 33

72 spikes on surface

Question 34

Where is the CD4 receptor site in HIV?

Answer 34

On gp120

Question 35

For HIV what is bound to diploid (+) ssRNA?

Answer 35

50 molecules of reverse transcriptase (RT) (+integrase & protease enzymes) (POL)

Question 36

For HIV, what does the p24 caspid protein (GAG) form?

Answer 36

A cone-shaped shell around the ribonucleoprotein

Question 37

For HIV, what doe the p17 matrix protein line?

Answer 37

The inner surface of the lipid envelope?

Question 38

For HIV what do p7 + p9 form?

Answer 38

Ribo-nucleoprotein complex with the RNA genome

Question 39

What are the general features of the HIV family?

Answer 39

Three main ORFs in RNa genome Reverse transcription generates Gag, Pol & Env in proviral DNA Encode internal structural proteins, enzymes and envelope proteins respectively

Question 40

What is the morphology of HIV-1?

Answer 40

Cirvular, conical capsid, distinctive Env

Question 41

What is CD4 expressed on?

Answer 41

Surface of T-helper lymphocytes

Question 42

What does HIV also infect?

Answer 42

``` Other cell types that have CD4 molecules on their surface E.g. B lymphocytes Macrophages Dendritic cells Brain cells ```

Question 43

Where is CD4 mainly found?

Answer 43

Th cells and macrophages

Question 44

What is CD4?

Answer 44

Primary HIV receptor

Question 45

What is CD4's normal cellular function?

Answer 45

To recognise Ag in association with class II MHC

Question 46

What binds to CD4?

Answer 46

Trimeric gp120 | Coreceptors (CXCR4, CCR5)

Question 47

What happens to CD4 in HIV?

Answer 47

Conformational change occurs (Gp41 transmem) Membrane fusion results between virus and cell HIV enters the cell

Question 48

What is the HIV replication cycle?

Answer 48

The HIV RNA genome is reverse transcribed into DNA (cytoplasm) This translocates to the nucleus Integrates into the host genome New viral RNA may be transcribed and proteins translated These can be packaged into particles and bud from the cell

Question 49

What is HIV life cycle?

Answer 49

``` Attachment Uncoating Reverse transcription Circularisation Integration Transcription Translation Core particle assembly Final assembly and budding ```

Question 50

What is replication of HIV?

Answer 50

``` Single stranded viral RNA Reverse transcriptase Viral DNA copy (proviral DNA) Integration into host cell chromosome Latency Virus gene expression and replication ```

Question 51

What is error prone in HIV causing variability?

Answer 51

RT enzyme

Question 52

What is the error rate within RT?

Answer 52

High= 1 in 3000 nucleotides

Question 53

What does RT lack?

Answer 53

3’-5’ exonuclease proof reading activity that excises mispaired nucleotides- DNA polymerases with proof-reading activity, has an error rate of 1 in 100,000

Question 54

What do polymerisation errors of RT cause?

Answer 54

Virus diversity

Question 55

What are HIV infection routes?

Answer 55

Transmission- body fluids containing HIV and /or infected T cells Main route is as a sexually transmitted disease (STD) Intravenous drug abuse or transfusion with contaminated blood products Mother- Baby