HIV and AIDS Flashcards
What is HIV?
Human Immunodeficiency Virus
How many people are infected with HIV?
30-80 million people infected
What does HIV cause?
AIDS
What is AIDS?
Acquired Immuno Deficiency Syndrome
Where did HIV begin?
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
What does HIV do?
Depletion of CD4+ T helper cells over 2-10 years
What does HIV lead to?
Opportunistic infections
E.g. recurrent pneumonia, bacterial & viral
Direct effect of virus (wasting syndrome, neurological)
What happens if a patient is left untreated with HIV?
Dies of diseases within 10 years
What happens in HIV in the first week of infection?
HIV replication
What happens during HIV within the first 6 weeks?
CD4+ cells depleted
What then occurs after 6 week in HIV?
Gradual increase in virus copy number after that
Gradual decrease in CD4 cells of immune system
What is HIV’s origins?
Central Africa roughly 100 years ago
What is HIV closely related to?
SIV from chimpanzees, gorillas and SMs (mild disease)
How was many of the original HIV cases obtained?
From eating or butchery
How many types of HIV are there?
HIV-1 (main) and HIV-2 (niche in sub-saharan Africa) exist and share approx. 40% similarity
What is HIV-1?
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
What is the most common type of HIV-1 in the UK?
Clade B
Where do most AIDS cases arise?
Developing countries (ART in the developed countries)
How many people are infected with AIDS?
60 million globally
How many people have died from AIDS in the last 30 years?
39 million
What is the difference between HIV-1 and HIV-2?
HIV-1 is responsible for > 99% of AIDS cases in the west
HIV-2 is less virulent
What do both HIV-1 and HIV-2 lead to?
AIDS (1>2)
How is HIV and AIDS transmitted?
Sexually, M-B blood-borne (parenterally)
What does HIV and AIDS lead to?
Chronic, persistent infection
How long can HIV/AIDS patients be symptomless?
10 years
What is the incidence of HIV-1 and AIDS?
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
What type of virus is HIV?
retrovirus
What are the retroviridae family?
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
What is the HIV genome?
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
What are the 3 mains ORFS (within genome HIV-1)?
Gag- capsid, nucleocaspid, matrix
(pro protease required for processing gag)
Pol- reverse transcriptase, RNase H and integrase
Env- envelope glycoproteins (SU (gpl120) & TM (gp41))
What are the two regulatory genes in LTR?
Tat- transcriptional regulation; binds TAR in LTR
Rev- Regulates viral mRNA production and nuclear export
What are the four accessory genes in LTR?
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
For HIV what do glycoproteins gp120+ gp41 (ENV) form?
72 spikes on surface
Where is the CD4 receptor site in HIV?
On gp120
For HIV what is bound to diploid (+) ssRNA?
50 molecules of reverse transcriptase (RT) (+integrase & protease enzymes) (POL)
For HIV, what does the p24 caspid protein (GAG) form?
A cone-shaped shell around the ribonucleoprotein
For HIV, what doe the p17 matrix protein line?
The inner surface of the lipid envelope?
For HIV what do p7 + p9 form?
Ribo-nucleoprotein complex with the RNA genome
What are the general features of the HIV family?
Three main ORFs in RNa genome
Reverse transcription generates Gag, Pol & Env in proviral DNA
Encode internal structural proteins, enzymes and envelope proteins respectively
What is the morphology of HIV-1?
Cirvular, conical capsid, distinctive Env
What is CD4 expressed on?
Surface of T-helper lymphocytes
What does HIV also infect?
Other cell types that have CD4 molecules on their surface E.g. B lymphocytes Macrophages Dendritic cells Brain cells
Where is CD4 mainly found?
Th cells and macrophages
What is CD4?
Primary HIV receptor
What is CD4’s normal cellular function?
To recognis Ag in assocn with class II MHC
What binds to CD4?
Trimeric gp120
Coreceptors (CXCR4, CCR5)
What happens to CD4 in HIV?
Conformational change occurs (Gp41 transmem)
Membrane fusion results between virus and cell
HIV enters the cell
What is the HIV replication cycle?
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
What is HIV life cycle?
Attachment Uncoating Reverse transcription Circularisation Integration Transcription Translation Core particle assembly Final assembly and budding
What is replication of HIV?
Single stranded viral RNA Reverse transcriptase Viral DNA copy (proviral DNA) Integration into host cell chromosome Latency Virus gene expression and replication
What is error prone in HIV causing variability?
RT enzyme
What is the error rate within RT?
High= 1 in 3000 nucleotides
What does RT lack?
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
What do polymerisation errors of RT cause?
Virus diversity
What are HIV infection routes?
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
