HIV and AIDs II

Question 1

Cytopathic, especially late in infection

Answer 1

HIV

Question 2

Cells infected by ‘late’ virus form syncytia which later die. Syncytium formation results from binding of SU/TM on infected cell plasma membranes to

Answer 2

CD4 membranes of other cells

Question 3

This triggers membrane fusion just as during virus infection, and allows virus to spread between cells without exposure to

Answer 3

Antibody

Question 4

HIV regulatory proteins, especially nef, have been reported to have

Answer 4

Toxic effects

Question 5

Blocks repair of DNA damage and un-repaired DNA may trigger apoptosis

Answer 5

Vpu

Question 6

Most dying T cells are not infected with

Answer 6

HIV

Question 7

Characterized by persistent high-level proliferation and activity of all types of immune cells and overproduction of their products (Ig, cytokines)

Answer 7

HIV

Question 8

This may favor virus replication which is more efficient in activated T cells, and/or lead to ‘activation-induced death’ of lymphocytes as they become progressively more susceptible to

Answer 8

Apoptosis

Question 9

Soluble SU protein can deliver signals through CD4 and CCR which may also favor

Answer 9

Apoptosis

Question 10

One mechanism by which HIV may escape the immune system is failure of the persistence of

Answer 10

CD8 anti-HIV clones

Question 11

Preferential infection of anti-HIV clones of CD4+ cells may also allow

Answer 11

HIV to evade immune system

Question 12

MHC heterozygosity and response to numerous HIV epitopes both slow the progression of

Answer 12

HIV

Question 13

“Co-factors” such as infections with other pathogens increase the rate of transcription from the HIV LTR by activating

Answer 13

T-cell transcription factors

Question 14

For example, development of active tuberculosis increases

Answer 14

Plasma viremia

Question 15

Progressive exhaustion of the immune system may eventually decrease CD4+ cell numbers to the point that immunity cannot be maintained, setting the stage for high-level

Answer 15

Viral multiplications

Question 16

Chronic exposure of T cells to antigen leads to appearance of membrane receptors (CD38, PD-1) that decrease their

Answer 16

Function

Question 17

Blockade of these receptors may be a promising approach to restoring immune control of

Answer 17

HIV

Question 18

Lacks the proofreading capacity of cellular DNA polymerases and has a high mutation rate, roughly 10-3 per nucleotide

Answer 18

Reverse transcriptase

Question 19

The transition from the asymptomatic period to AIDS is marked by a shift in co-receptor use and in

Answer 19

Cell tropism

Question 20

Initially HIV uses CCR5. Late in infection, virus variants appear which use CXCR4 and are highly-cytopathic for

Answer 20

T cells

Question 21

What is the standard screening process for HIV?

Answer 21

ELISA, then if positive, ELISA is repeated and confirmed by Western blot

Question 22

PCR tests are very sensitive and can be useful if Western Blots are ambiguous, but their sensitivity renders them prone to

Answer 22

False positives

Question 23

What is the current treatment for HIV?

Answer 23

Use of 2 nucleoside RT inhibitors plus a non-nucleoside RT inhibitor or protease inhibitor

Question 24

Chosen so that mutations which confer resistance to one drug do not create resistance to another

Answer 24

RT inhibitors

Question 25

Integrase inhibitors and CCR5 Chemokine receptor antagonists have recently been

Answer 25

FDA-approved

Question 26

Mediates fusion of the viral envelope with the plasma membrane and contains a pair of α-helices which undergo two shifts in conformation

Answer 26

HIV TM

Question 27

The first shift exposes a hydrophobic fusion peptide which inserts into the

Answer 27

Host cell membrane

Question 28

The second brings viral and host membranes close together, as a prelude to -Requires lateral association of α-helices

Answer 28

Fusion

Question 29

A synthetic α-helical peptide that binds to the intermediate conformation of TM, prevents the second shift, and blocks fusion

Answer 29

T-20

Question 30

In clinical trials it reduced viral load by about 100x and is FDA-approved

Answer 30

T-20

Question 31

For patients with low CD4 count, we want to give prophylaxis against Pneumocystis carinii pneumonia. For this, we give

Answer 31

TMP-SMX

Question 32

Can cause lipid redistribution and are linked to heart attacks

Answer 32

Protease inhibitors

Question 33

Nucleoside RT inhibitors can be

Answer 33

Nephrotoxic

Question 34

Indicates the patients current stage of disease

Answer 34

CD4 level

Question 35

Predicts how rapidly a patient’s disease is likely to progress

Answer 35

Viral load

Question 36

SU protein, the target of neutralizing antibodies, is heavily glycosylated, which shields most epitopes from

Answer 36

Antibodies

Question 37

Bind to a surface loop of SU, but this can rapidly develop amino acid substitutions which render existing antibodies ineffective

Answer 37

Neutralizing anti-bodies