HIV and AIDS Flashcards
What 2 rare, opportunistic infections in previously healthy men first sparked the first reposts of HIV?
Pneumocystis Carinii
Kaposi’s Sarcoma
What does HAART stand for and what is it?
Highly active anti-retro viral therapy = the use of multiple (3) drugs on viral targets for the treatment of HIV
Usually 2 NRTI’s and 1 NNRTI or 1 protease inhibitor
When was HAART first introduced?
Mid-90’s
What is a retrovirus?
It is an RNA virus that inserts a copy of its genome (genetic material) into the host cells DNA after invasion in order to replicate
What 3 groups of polyproteins does the RNA of retroviruses synthesise?
Name some of the enzyme groups within each.
1) Gag (group specific antigen) = matrixes, capsid, nucleocapsid
2) Pol (polymerases) = protease, reverse transcriptase, integrase
3) Env (envelope glycoproteins) = surface, transmembrane
What is seroconversion?
The time at when antibodies have been produced to the viral antigen and are detectable in the blood (blood test positive)
How long does seroconversion take?
Usually within the first 1-3 weeks
What is the name given to the flu like symptoms that occur within the first few weeks of HIV infection?
HIV prodrome
How does reverse transcriptase work?
Retrovirus RNA is reverse transcribed into cDNA which then integrates into the host cells genome in order to hijack and replicate
What name is given to a retrovirus after it has undergone reverse transcriptase and integrated into the host cell?
The retrovirus is now called a provirus
What is the consequence of integration of retroviruses into host cells?
What effect does this have on retroviral infection?
The infected cell can NOT be cured of the retroviral infection, the cell can only be destroyed by the killing of that cell
This means retroviral infections can not be cured and persist for life
Which cells does HIV infect? (E.g. which is it ‘tropic’ for)
Why is this?
Primarily CD4 T cells, but others too
The virus can only infect cells which have CD4 co-receptor (CD4 T cells, macrophages, monocytes and dendritic cells) as well as co-stimulators molecules such as CCR5/CXCR4, as these are required for membrane fusion and endocytosis
What 2 membrane proteins does HIV entry require?
1) CD4 protein
2) chemokine receptor (CCR5/CXCR4)
What is the name of the structure formed when CD4 and the chemokine receptor of the host cell and the HIV retrovirus bind, which allows the membranes to fuse and endocytosis to occur?
6-helix bundle formation
Does reverse transcriptase have a function to check its accuracy?
No, this allows mutations to occur
What are the 2 heterodimer polyprotein subunits of the RT enzyme?
P66 and P51
What are the 3 enzymatic activities of reverse transcriptase?
What does each do?
1) RNA-dependant DNA polymerase = synthesises DNA on virus RNA genome
2) RNAsH = cleaves RNA from the able RNA/DNA hybrid
3) DNA-dependant DNA polymerase = synthesises DNA from DNA
What is the name of the primer molecule for reverse transcription in HIV infection?
tRNAlys3
How does HIV lead to aids?
CD4 T cells are inexorably depleted by the virus as they inject and hijack the cells
What is viral load?
The number of viral RNA genomes per ml of blood
What areas and cells are the main primary targets of acute HIV infection?
CD4 T cells in the mucosa (where majority of CD4 T cells live)
Gut assisted lymphoid tissue (GALT) = T cell nodes eradicated
Which host cell protein interferes with HIV entry?
Which virally encoded protein counteracts the activity of this protein?
SERINC (serine inclusion into phospholipids)
Counteracted by NEF
Which host cell protein inhibits HIV release from the cell surface?
Which virally encoded protein counteracts the activity of this protein?
Tetherin
VPU
Which host cell protein catalyses C to U to inhibit RT?
Which virally encoded protein counteracts the activity of this protein?
APOBEC3
VIF
Which host cell protein hydrolysis dNTP’s to inhibit RT?
Which virally encoded protein counteracts the activity of this protein?
SAMHD1
VPX
What is the main way HIV is transmitted?
Via mucosal routes
Over what time frame does a normal person (professor) progress to AIDS from HIV infection?
8-10 years
Over what time frame does a rapid person (professor) progress to AIDS from HIV infection?
1-3 years
Over what time frame does a long term non-progressor person (professor) progress to AIDS from HIV infection?
Remains AIDS free indefinitely
Over what time frame does a elite controller progress to AIDS from HIV infection?
Aids free indefinitely AND <50 copies RNA/ml of blood
What causes the acute drop in viral load just after acute infection?
CD8 T cells killing infected CD4 T cells
How is HIV diagnosed?
ELISA testing for anti-p24 (capsid) antibodies in the serum in those who have seroconverted
Does a negative ELISA HIV test mean a person does not have HIV?
No, they may have just not seroconverted
Which test can confirm HIV and level of viral loads before seroconversion?
RT-PCR
What causes karposi’s sarcoma?
Human herpes virus 8
What is pneumocystis carinii?
A fungal pneumonia
How does maraviroc work?
Binds to CCR5 co-receptor to prevent virus interaction with host cell
How does enfirvitide (T20) work?
Prevents fusion of two membranes between HIV and host cells
What are the two types of RT inhibitor drugs and how do each work
1) Nucleoside analogue reverse transcriptase inhibitors (NRTI) = act as a nucleoside lacking functional group to allow virus chain to grow, therefore terminate chain short
2) Non-nucleoside reverse transcriptase inhibitors (NNRTI) = bind to RT (away from active site) causing conformational change and block it’s action
How does raltegravir work?
Is an integrase inhibitor, stopping cDNA from virus integrating with host cell DNA
How do protease in inhibitors work?
Stop Gag and Pol proteins, meaning new viruses are created but are non-infectious
What needs to happen to latent infected cells to cure HIV?
We need a drug to shock and kill them, i.e. wake them up, get the, to start transcription of new virus particles and kill them, all while the patient is taking a HAART
What is an ‘undetectable’ viral load (which is also the aim of treatment)?
<50 cpm (copies per ml)
At what CD4 count do most AIDS diagnoses occur?
<200 cpm
What CD4 count gives a HIV+ person the same survival rate as the general population?
CD4 count >500cells/ml for >5 years
When should we be targeting people for HIV blood test screening?
What % are we currently screening and what is the % target?
On A&E admission
We are currently hovering around 60-70% but are aiming for 85%
