HIV Flashcards by Olivia Galante

What family of viruses does HIV belong to?

retroviridae

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What is the capsid symmetry of HIV?

icosahedral

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Does HIV have an envelope?

yes

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What is the genome of HIV?

+ sense ssRNA

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Where does the genome of HIV replicate?

in the nucleus

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Where is virus assembly of HIV?

in the cytoplasm

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What are the 3 major genes of the HIV genome?

gag, pol and env

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What is encoded by the gag gene?

the matrix, capsid and nucleocapsid

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What is encoded by the env gene?

the surface glycoprotein (SU or gp120) which binds to the CD4 receptor and the transmembrane protein (TM or gp41) which enables the virus to attach to target cells

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What is encoded by the pol gene?

reverse transcriptase, protease and integrase

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How does HIV enter cells?

the surface glycoprotein binds to the CD4 receptor which induces structural changes in the protein - this leads to exposure of coreceptor binding sites which bind to CCR5 or CXCR4 which leads to structural rearrangement and membrane fusion

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What is the difference between CCR5 and CXCR4 binding HIV?

CCR5 binding happens early in the infection and has less pathogenicity

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Why is there a high level of mutation in HIV?

because the reverse transcriptase is highly error prone

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What is the role of integrase?

catalyses the random integration of HIV DNA into cell DNA which is required for the production of new virus

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What is the LTR and what is its role?

the LTR is a long terminal repeat on both ends of the viral DNA which binds to integrase so the DNA can be integrated into the host DNA - it is important because the 5’ LTR acts as a promoter and is activated by NFkappaB when T cells are activated - therefore T cell activation results in transcription of viral proteins

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What is the function of the tat protein?

binds to TAR (transactivating response element) which is essential for efficient transcription and also has a role in phosphrylating RNA polymerase II to make it an efficient enzyme

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What is the function of the rev protein?

allows fragments of HIV mRNA that contain a HIV Rev response element (RRE) to be exported from the nucleus to the cytoplasm

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Are tat and rev essential for HIV replication?

yes

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Are vif, vpr, vpu and nef essential for HIV replication?

no - but they are essential for pathogenesis

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What is the role of vif?

blocks APOBEC (an enzyme which mutates viral DNA)

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What is the role of vpr?

nuclear import of DNA

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What is the role of nef?

down regulates MHC class I

What is the role of vpu?

down regulates MHC class I and counteracts tetherin (a protein which prevents the release of viral particles)

How does tat down regulate MHC class I?

by blocking transcription

What is involved in the maturation of HIV particles?

the gag-pol precursor acts as a protease which cleaves the polyproteins into individual proteins

What is viral latency?

the HIV lies dormant and hidden in T cells so that when patients come of HAART the virus can come back - latency is the barrier to curing HIV

What are the 3 phases of untreated HIV?

primary infection where there is a big increase in the amount of virus and a plunge in the number of CD4 cells, asymptomatic infection where there is a stabilisation of the amount of virus and the number of CD4 cells and then the symptomatic infection and AIDS where there is a decline in the number of CD4 cells and increase in the number of virus

What are the clinical features of primary HIV?

* Fever * Myalgia/arthralgia * Nausea/vomiting/diarrhoea * Weight loss * Malaise/lethargy * Rash * Lymphadenopathy * Pharyngitis * Oral thrush * Headache/retro-orbital pain * Meningitis * Transient CD4 depletion

What happens in the gut in primary HIV?

there is loss of peyer's patches and a breakdown of gap junctions in gut epithelial cells

What is the incubation period of HIV?

2-4 weeks

How long does the clinical illness of primary HIV last?

1-4 weeks

How long after infection can an HIV p24 antigen be detected?

from 20-60 days

How long after infection can HIV RNA be detected?

between day 1 and day 18

How long after infection can HIV antibodies be detected?

40-50 days

Do HIV antibodies neutralise the virus?

no because of high levels of envelope glycosylation

Why does HIV escape the immune system?

because there are high levels of sequence variation, because of down regulation of MHC class I, because of loss of effector cells (CD4 cells), because of viral latency and because of priveleged sites of viral replication (the brain)

Why is it so difficult to make a vaccine for HIV?

because the envelope gp120 protein has so much variability and there are glycans masking the envelope

What is a predictor of survival in untreated HIV?

the viral load during the quasi steady state where viral production is equal to viral clearance

What are the 3 causes of T cell depletion?

CD4 T cell destruction, chronic immune activation and impaired T cell production

What is the attenuated strain of HIV?

where the nef gene has been deleted so its less pathogenic

What is the viral R5 phenotype?

where the virus is able to alter is envelope so its more pathogenic

What is the result of a CCR5 mutation in the host?

resistance to HIV

What is HAART?

highly active anti retro-viral therapy

How is development of drug resistance minimised?

by using 3 different anti virals in combination

What are the different anti retro viral therapies for HIV?

nucleoside reverse transcription inhibitors, nucleotide reverse transcription inhibitors, non nucleoside reverse transcription inhibitors, entry inhibitors, protease inhibitors and integrase inhibitors

What different entry inhibitors are there?

coreceptor antagonists and enfuviritide which prevents the molecular gymnastics to stop fusion

What is the mechanism of action of nucleoside reverse transcription inhibitors?

the drugs are analogues of nucleosides but lack the 3' hydroxyl group - they are prefentially used by the virus in replication but because of the lack of the 3' hydroxyl group they prevent chain elongation

What is the mechanism of action of non nucleoside reverse transcriptase inhibitors?

directly inhibit the reverse transcriptase enzyme

What is the mechanism of action of raltegravir?

it is an integrase inhibitor - it blocks the strand transfer step of integration

What is the mechanism of action of protease inhibitors?

inhibits maturation of the HIV particle by binding and inhibiting the protease enzyme

Why does HAART fail to cure HIV?

because a small proportion of HIV remains latent

What causes the non AIDS co morbidities of HIV?

chronic inflammation

What are the non AIDS co morbidities of HIV?

cardiovascular disease, cancer, osteoporosis, liver failure, kidney failure, cognitive decline, frailty