HIV

Question 1

What does Gag do

Answer 1

Gag: group specific antigen.

Viral core proteins: MA (matrix), CA (capsid), NC (nucleocapsid) - formation of the inside part of the virus

Question 2

What does Pol do

Answer 2

Pol: polymerase
Enzymes: PR (protease), RT (reverse transcriptase), IN (integrase) - converting viral RNA into double stranded DNA

Question 3

What does Env do

Answer 3

envelope glycoprotein

Su (surface), TM (transmembrane) - interaction with hsot receptors and infection into the cell

Question 4

What does reverse transcriptase do

Answer 4

copying of an RNA template (the viral genome) into a double stranded DNA copy

Question 5

What is integration

Answer 5

covalent insertion of viral cDNA into the genome of the infected cell, to form the provirus

Question 6

What is the consequence of integration

Answer 6

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

Question 7

What is the outer layer of the HIV virus

Answer 7

lipid bilayer with protruding Env spikes (heterodimer of trimers SU3TM3). Surface and transmembrane proteins.

Question 8

What is the inner layer of the HIV virus

Answer 8

Gag proteins. In the immature particle, Gag itself forms a single shell.

Question 9

What is the the mature particle

Answer 9

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)

Question 10

Describes the steps of viral replication

Answer 10

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

Question 11

What does CD4 binding cause

Answer 11

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

Question 12

What is reverse transcriptase

Answer 12

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.

Question 13

What clade dominates in southern afria

Answer 13

Clade C

Question 14

What clade dominates in europe

Answer 14

Clade B

Question 15

What clade dominates in northern africa

Answer 15

Clade A

Question 16

What does APOBEC do

Answer 16

converts cytosine to uracil within RNA leading to additional mutations. This is an anti-viral strategy as stop codons could be made.

Question 17

What is the in-vitro ranking of HIV-1 regulatory proteins

Answer 17

Tat/Rev>Vif>Nef>Vpr/Vpu

Question 18

What does tat do

Answer 18

Potent activator of viral transcription

Question 19

What does rev do

Answer 19

mediates unspliced RNA nuclear export

Question 20

What does vif do

Answer 20

critical regulator of virus infectivity. Acts against APOBEC gene. Stops introduction of additional mutations.

Question 21

What does nef do

Answer 21

immune modulator, T-cell activation, virus infectivity. Remove CD4 from surface of the cell.

Question 22

What does vpu do

Answer 22

immune modulator, virus release. Tetherin prevents virus from being released. Vpu marks tetherin for destruction.

Question 23

What does vpr do

Answer 23

ell cycle, virus nuclear import

Question 24

What does SAMHD1 sdo

Answer 24

suppresses RT in myeloid cells by hydrolysing dNTPS

Question 25

What does SERINC do

Answer 25

Interfere with viral entry

Question 26

What is the most common combination of HAART

Answer 26

2* NRTI and 1 NNRTI or Protease inhibitor

Question 27

What are latent viral reservoirs

Answer 27

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.

Question 28

What is associated with elite control

Answer 28

HLA B57 or B 27 - HLA molecule has mutation in tail region so nef can’t remove it from the cell surface

Question 29

What are CRR5 inhibitors

Answer 29

(chemokine receptor antagonist) - Maraviroc

Question 30

What are fusion inhibitors

Answer 30

Enfurvitide. Targets envelope protein once it’s bound to CD4.

Question 31

What are RT inhibitors

Answer 31

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.

Question 32

What are integrase inhibitors

Answer 32

raltegravir - blocks strand transfer reaction

Question 33

What is acute infection controlled by

Answer 33

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

Question 34

How is HIV diagnosed

Answer 34

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

Question 35

What is one of the most common causes of cancer in people with HIV

Answer 35

Kaposi’s Sarcoma - herpes virus 8, fungal pneumonia, toxoplasmosis

Question 36

What is a major target in acute HIV-1 function

Answer 36

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