HIv

Question 1

HIV-1 evolved from a lentivirus found in monkeys called ______

Answer 1

SIV

Question 2

what are the key points to the HIV virus

Answer 2

• double stranded RNA genome
• integrated into host genome
• when activated many copies are produced by an error prone reverse transcriptase
• packages and secreted by host cell
• virus can be dormant when integrated for long periods of time

Question 3

what are the regulatory proteins of HIV and what do they do

Answer 3

TAT - transactivator of HIV promoter

REV - nuclear export of late unspliced RNA to cytoplasm

Question 4

what are the accessory proteins of HIV and what do thet do

Answer 4

VIF, VPR and VPU act as adapter to cause E3 ubiquitin ligase to target viral defence particles
VPU and NEF down regulate CD4 assisting viral release to other target cells

Question 5

what are the target cells for the HIV virion

Answer 5

CD4 T cells
macrophages
dendritic cells

Question 6

how does HIV fuse to the membrane of cells

Answer 6

via gp120/gp41 spike

Question 7

what does gp120 interact with on target cells

Answer 7

CD4 and accessory protein CCR5

Question 8

how many gp41 are there in the complex of gp41/gp120

Answer 8

3

Question 9

what happens once the virus has attached to the target cell

Answer 9

reverse transcription of genome from RNA to cDNA

migration to nucleus and integration into host genome

Question 10

what happens after the HIV genome enters the host genome

Answer 10

expression of viral particles
generation of viral RNA genome and encapsulation
expression of env protein and cleavage to gp120 and gp41
secretion of mature virions from cell surface

Question 11

what are the effects of infection by the HIV virion

Answer 11

increased apoptosis of target cells

targetting of infected cells by CD8 cytotoxic T cells

Question 12

what is the acute phase of infection of HIV virion

Answer 12

CD4 cells are depleted by cytotoxic T cells. initially they recover as HIV evades immune system

Question 13

what does slow depletion of CD4 T cells due to generalised immune activation and loss of ability to produce CD4 T cells lead to

Answer 13

level of CD4 T cells falling below a critical level and immune system becoming compromised

Question 14

why is HIV so difficult to eradicate

Answer 14

HIV-1 attacks cells of the immune system
accessory proteins downregulate the immune response
HIV can be dormant for long periods evading the immune system and creating a reservoir of virus

Question 15

what is the current treatment for HIV

Answer 15

triple therapy

AZT

Question 16

triple therapy is an aggressive treatment using what

Answer 16

inhibitors of membrane fusion/infection
inhibitors of reverse transcriptase
inhibitors of integration
protease inhibitors which prevent the maturation of viral proteins (gp120/gp41)

Question 17

antibodies can be cloned from long term supressor patients and expressed in a recombinant form to target what

Answer 17

gp120 stalk and block infection

Question 18

what are the key features of HIV that hinder the immune response

Answer 18

genetic variability
immunodominance and cryptic factors
immunosupressive factors

Question 19

there is a high genetic variability of HIV even within individuals. what is this due to

Answer 19

error prone reverse transcriptase

Question 20

what can the high genetic variability of HIV lead to

Answer 20

resistance to antiviral drugs arising

Question 21

Patients will either fail to develop a neutralising antibody or cellilar immune response OR

Answer 21

HIV mutates and evades the immune system

Question 22

what does HIV mutating a lot provide conditions to happen

Answer 22

natural selection to develop novel variants

Question 23

evidence suggests what is a key target for preventing infection

Answer 23

spike of gp120/gp41

Question 24

what does gp120 have recognition sites for

Answer 24

CD4 and CCR5

Question 25

by blocking the sites of gp120 you can

Answer 25

sterically inhibit binding of CD4 and infection

Question 26

what is the problem of blocking the CD4 and CCR5 binding sites of gp120

Answer 26

they are not exposed to the immune system. only transiently expressed as a result of CD4 binding. and immunoglobulins are too large to access sites

Question 27

what is a further problem with creating therapies to target gp120

Answer 27

gp120 features a number of solvent exposed peptide loops that are highly variable. they are preferred immunodominant targets for B cell responses and act as decoys

Question 28

what is sterilising immunity

Answer 28

Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host.

Question 29

elimination of HIV may well be impossibles so strategies must shift to attempting to

Answer 29

reducing spread of HIV by reducing the viraemia

Question 30

evidence from non progressors suggest that which type of antibodies exist

Answer 30

natural neutralising antibodies

Question 31

it is likely that protection will require what

Answer 31

both neutralising antibody and Cytotoxic T cell responses

Question 32

what was a breakthrough in HIV vaccines compared to previous attempts

Answer 32

AIDSVAX/ALVAC - infection rate approx 30% lower in volunteers

Question 33

what are the future trends in HIV vaccination

Answer 33

exploit natural non progressors
clone their antibodies
broadly neutralising
use these in a passive immunisation approach to decrease viral load
reduce viraemia and this halts transmission