HIV Flashcards
What does Gag do
Gag: group specific antigen.
Viral core proteins: MA (matrix), CA (capsid), NC (nucleocapsid) - formation of the inside part of the virus
What does Pol do
Pol: polymerase
Enzymes: PR (protease), RT (reverse transcriptase), IN (integrase) - converting viral RNA into double stranded DNA
What does Env do
envelope glycoprotein
Su (surface), TM (transmembrane) - interaction with hsot receptors and infection into the cell
What does reverse transcriptase do
copying of an RNA template (the viral genome) into a double stranded DNA copy
What is integration
covalent insertion of viral cDNA into the genome of the infected cell, to form the provirus
What is the consequence of integration
an infected cell cannot be cured of retroviral infection, other than by killing that ell. This makes it impossible to eradicate naturally an infected animal or a retroviral infection
What is the outer layer of the HIV virus
lipid bilayer with protruding Env spikes (heterodimer of trimers SU3TM3). Surface and transmembrane proteins.
What is the inner layer of the HIV virus
Gag proteins. In the immature particle, Gag itself forms a single shell.
What is the the mature particle
MA associates with the membrane, CA forms the conical capsid, and NC coats the viral RNA genome. The core contains two genomic RNA strand, tRNALys3, and about 50 copies of each viral enzyme (PR, RT and IN)
Describes the steps of viral replication
Attachment and receptor binding. CD4 and co receptors CXCR4 and CCR5
Membrane fusion - allow entry of the core of virus
Uncoating and reverse transcription - minimise immune response
Nuclear import
Integration of DNA into genome
Allows transcription of viral genes and RNA processing
Nuclear export
Translation
Assembly
Budding
Maturation
What does CD4 binding cause
conformational rearrangement of the protein to revela co-receptor binding site. New binding sites can be used for HAART.
After co receptor binding, more rearrangement. Fusion peptide inserts into viral membrane. Creates 6-helix bundle formation to allow membrane fusion
What is reverse transcriptase
heterodimer of p66 and p51
RT displays three distinct enzymatic activates:
RNA dependent DNA polymerase - coverts viral RNA into cDNA
RNAasH (cleaves RNA from RNA/DNA hybrid)
DNA-dependent DNA polymerase - makes double strand.
What clade dominates in southern afria
Clade C
What clade dominates in europe
Clade B
What clade dominates in northern africa
Clade A
What does APOBEC do
converts cytosine to uracil within RNA leading to additional mutations. This is an anti-viral strategy as stop codons could be made.
What is the in-vitro ranking of HIV-1 regulatory proteins
Tat/Rev>Vif>Nef>Vpr/Vpu
What does tat do
Potent activator of viral transcription
What does rev do
mediates unspliced RNA nuclear export
What does vif do
critical regulator of virus infectivity. Acts against APOBEC gene. Stops introduction of additional mutations.
What does nef do
immune modulator, T-cell activation, virus infectivity. Remove CD4 from surface of the cell.
What does vpu do
immune modulator, virus release. Tetherin prevents virus from being released. Vpu marks tetherin for destruction.
What does vpr do
ell cycle, virus nuclear import
What does SAMHD1 sdo
suppresses RT in myeloid cells by hydrolysing dNTPS
What does SERINC do
Interfere with viral entry
What is the most common combination of HAART
2* NRTI and 1 NNRTI or Protease inhibitor
What are latent viral reservoirs
barrier to an HIV cure is the integrate provirus.
ART prevents new cell infection
Some cells don’t die and fall back to a resting state - not actively producing virus but have HIV genome introduced. Have silent HIV transcription. Latent pool persists in the presence of drugs. After drug removal, there is activation stimulus so there will be viral rebound.
What is associated with elite control
HLA B57 or B 27 - HLA molecule has mutation in tail region so nef can’t remove it from the cell surface
What are CRR5 inhibitors
(chemokine receptor antagonist) - Maraviroc
What are fusion inhibitors
Enfurvitide. Targets envelope protein once it’s bound to CD4.
What are RT inhibitors
nucleoside analogues reverse transcriptase inhibitors (NRTI) - no 3’OH leads to chain termination (e.g. Zidovudine; Lamivudine. Non-nucleoside reverse transcriptase inhibitors (NNRTI) - Allosteric RT inhibitors - do not bind to active site. Blocks initiation of RT e.g. Efavirenz and nevirapine.
What are integrase inhibitors
raltegravir - blocks strand transfer reaction
What is acute infection controlled by
Acute infection is controlled by a strong CD8 T cell response
Then produce non-neutralising anti-Env antibodies
Then neutralising anti-Env antibodies
Because virus is mutating at such a fast rate, it prevents the antibodies from working
How is HIV diagnosed
ELISA test for presence of anti-p24 antibodies in the serum. Only detects individuals who have seroconverted
A positive sample is retested using a different ELISA or Western Blot
Confirmation by quantitative reverse transcription linked polymerase chain reaction to detect HIV genomic RNA in the blood
What is one of the most common causes of cancer in people with HIV
Kaposi’s Sarcoma - herpes virus 8, fungal pneumonia, toxoplasmosis
What is a major target in acute HIV-1 function
Gut-associated lymphoid tissue is the major target tissue in the acute HIV-1 function
HIV spreads rapidly to the CD4 T cells in the lymphoid tissue of the guy
GALT is virtually denuded of T cells
Immune integrity of GALT never recovers, even during therapy
