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Flashcards in HIV and AIDS Deck (55)
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1
Q

What is HIV?

A

Human Immunodeficiency Virus

2
Q

How many people are infected with HIV?

A

30-80 million people infected

3
Q

What does HIV cause?

A

AIDS

4
Q

What is AIDS?

A

Acquired Immuno Deficiency Syndrome

5
Q

Where did HIV begin?

A

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

6
Q

What does HIV do?

A

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

7
Q

What does HIV lead to?

A

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

8
Q

What happens if a patient is left untreated with HIV?

A

Dies of diseases within 10 years

9
Q

What happens in HIV in the first week of infection?

A

HIV replication

10
Q

What happens during HIV within the first 6 weeks?

A

CD4+ cells depleted

11
Q

What then occurs after 6 week in HIV?

A

Gradual increase in virus copy number after that

Gradual decrease in CD4 cells of immune system

12
Q

What is HIV’s origins?

A

Central Africa roughly 100 years ago

13
Q

What is HIV closely related to?

A

SIV from chimpanzees, gorillas and SMs (mild disease)

14
Q

How was many of the original HIV cases obtained?

A

From eating or butchery

15
Q

How many types of HIV are there?

A

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

16
Q

What is HIV-1?

A

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

17
Q

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

A

Clade B

18
Q

Where do most AIDS cases arise?

A

Developing countries (ART in the developed countries)

19
Q

How many people are infected with AIDS?

A

60 million globally

20
Q

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

A

39 million

21
Q

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

A

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

HIV-2 is less virulent

22
Q

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

A

AIDS (1>2)

23
Q

How is HIV and AIDS transmitted?

A

Sexually, M-B blood-borne (parenterally)

24
Q

What does HIV and AIDS lead to?

A

Chronic, persistent infection

25
Q

How long can HIV/AIDS patients be symptomless?

A

10 years

26
Q

What is the incidence of HIV-1 and AIDS?

A

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

27
Q

What type of virus is HIV?

A

retrovirus

28
Q

What are the retroviridae family?

A

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

29
Q

What is the HIV genome?

A

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

30
Q

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

A

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

31
Q

What are the two regulatory genes in LTR?

A

Tat- transcriptional regulation; binds TAR in LTR

Rev- Regulates viral mRNA production and nuclear export

32
Q

What are the four accessory genes in LTR?

A

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

33
Q

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

A

72 spikes on surface

34
Q

Where is the CD4 receptor site in HIV?

A

On gp120

35
Q

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

A

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

36
Q

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

A

A cone-shaped shell around the ribonucleoprotein

37
Q

For HIV, what doe the p17 matrix protein line?

A

The inner surface of the lipid envelope?

38
Q

For HIV what do p7 + p9 form?

A

Ribo-nucleoprotein complex with the RNA genome

39
Q

What are the general features of the HIV family?

A

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

40
Q

What is the morphology of HIV-1?

A

Cirvular, conical capsid, distinctive Env

41
Q

What is CD4 expressed on?

A

Surface of T-helper lymphocytes

42
Q

What does HIV also infect?

A
Other cell types that have CD4 molecules on their surface
E.g. B lymphocytes 
Macrophages
Dendritic cells
Brain cells
43
Q

Where is CD4 mainly found?

A

Th cells and macrophages

44
Q

What is CD4?

A

Primary HIV receptor

45
Q

What is CD4’s normal cellular function?

A

To recognise Ag in association with class II MHC

46
Q

What binds to CD4?

A

Trimeric gp120

Coreceptors (CXCR4, CCR5)

47
Q

What happens to CD4 in HIV?

A

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

48
Q

What is the HIV replication cycle?

A

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

49
Q

What is HIV life cycle?

A
Attachment
Uncoating
Reverse transcription
Circularisation
Integration
Transcription
Translation
Core particle assembly
Final assembly and budding
50
Q

What is replication of HIV?

A
Single stranded viral RNA
Reverse transcriptase
Viral DNA copy (proviral DNA)
Integration into host cell chromosome
Latency
Virus gene expression and replication
51
Q

What is error prone in HIV causing variability?

A

RT enzyme

52
Q

What is the error rate within RT?

A

High= 1 in 3000 nucleotides

53
Q

What does RT lack?

A

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

54
Q

What do polymerisation errors of RT cause?

A

Virus diversity

55
Q

What are HIV infection routes?

A

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