Secondary immunodef Q

Macrophage-tropic **HIV** variants bind to which co-receptor?

a. CD28

b. CCR5

c. T-cell receptors (TCRs)

d. CXCR4

b

Fusion of HIV with the host-cell membrane requires the interaction of gp120 with which of the following?

a. CD4

b. human chemokine receptors

c. co-stimulatory molecules

d. T-cell receptors (TCRs)

a, b

A mutation in the gene encoding the Rev protein would result in which of the following?

a. formation of a provirus

b. retention of viral mRNAs in the nucleus

c. loss of reverse transcriptase activity

d. cessation of viral RNA transcription

b

Individuals who are resistant to **HIV** infection show a homozygous deficiency of which one of the following host proteins?

a. CXCR4

b. CCR5

c. gp120

d. CD4

b

In a certain phase of **HIV** infection, acute viremia is usually present and anti-**HIV** antibodies are first detected in the blood. What is this phase called?

a. the asymptomatic period

b. AIDS

c. seroconversion

d. clinical latency

c

Progression to **AIDS** is enhanced by which of the following?

a. HLA-B\*27

b. low-expressing allotypes of KIR3DL1 and HLA-B\*27

c. high-expressing allotypes of KIR3DL1 and HLA-B\*57

d. HLA-B\*57

e. HLA homozygosity

e

What occurs after reverse transcriptase copies the RNA genome of a **retrovirus** into a double-stranded complementary DNA (cDNA)?

a. The cDNA undergoes splicing to provide a mature mRNA for viral protein synthesis.

b. The cDNA is packaged into infectious virions.

c. The cDNA is transcribed to form mRNAs encoding viral proteins.

d. The cDNA is integrated into the genome of the host cell and forms a provirus.

d

Which one of the following individuals is able to reduce **HIV** to undetectable levels in the blood and remain healthy for decades?

a. a viremic controller

b. an elite controller

c. an HLA homozygous individual

d. a *CCR5*-Δ32 heterozygous individual

b

Cells that are susceptible to **HIV** infections express which one of the following **virus**-specific receptors on their surfaces?

a. gp120

b. CD4

c. gp41

d. CD8

b

In the absence of treatment, most people infected with **human immunodeficiency virus**-1 (**HIV**-1) succumb to which disease?

a. acquired immune deficiency syndrome

b. lymphoproliferative disorder

c. leukocyte depletion syndrome

d. HIV-induced viremia syndrome

a

Which one of the following is a type of RNA **virus** that replicates via a DNA intermediate?

a. a retrovirus

b. influenza virus

c. vaccinia virus

d. Epstein–Barr virus

a

Which one of the following will be significantly increased within days of an **HIV** patient’s receipt of an antiviral drug?

a. number of CD4 T cells

b. number of CD8 T cells

c. level of viral RNA in the blood

d. number of drug-resistant HIV variants

a

What is the source of RNA polymerase that is used for the transcription of a retroviral **provirus**?

a. RNA polymerase coded by the provirus

b. RNA polymerase transported into the infected cell by the virion

c. RNA polymerase provided by the host cell

d. virus-encoded RNA polymerase

c

Why is eradication of an **HIV** infection rare?

a. The virus undergoes a high rate of mutation during infection.

b. HIV rapidly incapacitates the immune system before adaptive immunity is stimulated.

c. There are no antiviral drugs available for HIV.

d. HIV peptides do not bind to MHC class I molecules.

a

The rate of transcription of viral RNAs from the **HIV** **provirus** is regulated by which of the following?

a. reverse transcriptase

b. Rev protein

c. gp120

d. Tat protein

d

What is the most common type of pathogen that causes disease in individuals with **AIDS**?

a. a drug-resistant pathogen

b. a pathogen that coexists with replicating HIV inside infected macrophages

c. an opportunistic pathogen

d. a new pathogen to which the patient has not developed a memory response

c

**Anti-retroviral therapy** (**ART**) involves which of the following?

a. a reverse transcriptase inhibitor that stops cDNA synthesis

b. a combination of antiviral drugs used together to prevent the generation of drug-resistant virus variants

c. a protease inhibitor that is highly resistant to cellular degradation and drug-detoxification enzymes

d. broadly neutralizing antibodies

b

Co-receptor commonly used by ‘macrophage-tropic’ HIV variants

CCR5

Integrates viral DNA into host chromosomal DNA

Integrase

Copies viral RNA genome into double stranded DNA

Reverse transcriptase

Primary host-cell receptor for HIV

CD4

Co-receptor commonly used by ‘lymphocyte-tropic’ HIV variants

CXCR4

Which of the following are ways in which HIV is transmitted to healthy individuals?

\
a. sexual intercourse

b. kissing

c. contaminated intravenous syringes

d. sweat

e. transfusion of blood or blood components

f. mosquitoes

g. breast-feeding

a, c, e, g

What of the following are true of most broadly neutralizing antibodies?

a. They acquire insertions in the variable regions of their heavy chains.

b. They are made by elite neutralizers.

c. They acquire somatic mutations only in the CDR loops.

d. They recognize highly conserved epitopes on HIV glycoproteins.

e. They are made during the primary immune response to HIV.

f. They bind to highly variable regions of HIV that have mutated.

g. They are polyreactive.

a, b, d

What happens to the RNA after a retroviral provirus is transcribed?

a. It is used as the genome to form infectious virions.

b. It is translated to produce viral proteins.

c. It must be converted to a complementary RNA form before it can be packaged to form an infectious virion.

d. It is converted to DNA by reverse transcriptase, and the DNA then integrates into the host-cell chromosome.

a, b

Fusion of HIV with the host-cell membrane requires the interaction of gp120 with which two of the following?

\
a. human chemokine receptors

b. T-cell receptors (TCRs)

c. CD4

d. co-stimulatory molecules

a, c

Which gene codes for core proteins and matrix proteins?

gag

Which gene codes for enzymes: reverse transcriptase, protease and integrase?

pol

Which gene codes for the transcriptional regulator?

tat

Which gene codes for viral spike envelope: gp120, gp41, glycoproteins and co-receptor for CD4?

env

Which gene codes for the protein that controls export of transcripts from the nucleus?

rev

What gene codes for a protein that influences particle infectivity?

vif

Which gene codes for the protein that facilitates viral replication (downregulates CD4, MHC class I and MHC class II)?

nef

Which gene promotes CD4 degradation and release of HIV-1 from cells?

vpu

Which gene arrests cell cycle, transports DNA to nucleus and influences virion production?

vpr

Which gene enhances HIV-2 replication by countering host factor SAMHD1?

vpx

Which gene is not found in HIV-1?

vpx

Which gene is not found in HIV-2?

vpu

What polymorphisms influence the progression of HIV to AIDs?

HLA and KIR

Combinations of which HLA and KIR genes are associated with different rates of progression?

Bw4+ HLA-B and KIR3DL1/S1

What is the most favourable HLA-B and KIR combination?

HLA-B\*57 with highly expressed KIR3DL1

What individuals suppress infection and maintain their health?

elite and viraemic controllers

Which HLA-B and KIR combination has the fastest progression to AIDs?

HLA-Bw4-80I with KIR3DL1I

Which HLA-B allotype shares the Bw4 epitope and the ligand for the NK-cell receptor KIR3DL1 (3DL1)?

B27 and B57

What glycoprotein binds to CD4 enabling **HIV** to attach to cells expressing **CD4**?

gp120

Which cells express CD4 and are therefore vulnerable to HIV?

Macrophages, dendritic cells and CD4 T cells

What is the primary receptor for HIV?

CD4

Which chemokine receptors are co-receptors for HIV infection?

CCR5, CSCR4

What enables gp120 to bind to the co-receptors CCR5 or CXCR4?

gp120 binding to CD4

What does the binding of gp120 lead to that causes the fusion of the viral envelope with the plasma membrane and release of the viral core into the cytoplasm?

release of gp41

Activation of what leads to low-level transcription of the provirus into mRNA that directs the synthesis of the early proteins Tat and Rev?

T cells

What happens when you have HLA homozygosity?

Hastens the progression to AIDs

What happens the more HLA molecules an individual expresses, the greater the likelihood?

of those molecules binding to **HIV**-derived peptides that stimulate effective **CD8** T-cell responses.

What two drugs are involved in ART?

Protease and reverse transcriptase inhibitors

Why do individuals who lack CCR5 are protected from HIV infection?

CCR5 is used by macrophage-tropic variants which initiate **HIV** infection

What do retroviral proviruses rely on provided by host cell?

Transcriptional and translational machinery

Why do high mutation rates associated with retroviruses?

reverse transcriptase is error-prone compared with DNA polymerases

How does the **virus** to keep ahead of adaptive immune responses during the course of the infection?

As mutations accumulate, new viral variants (quasi-species) arise and coexist

What HIV variant facilitates person-to-person infection?

Macrophage-tropic

What HIV variant is associated with the progression of infection to AIDS?

Lymphocyte-tropic

What is a provirus?

DNA form of a **retrovirus** following its insertion into the genome of the host cell.

When does reverse transcription of the retroviral RNA genome occur?

before integration into the host chromosome

Why is no further modification necessary to the RNA produced by the transcription of a **provirus**?

identical to the RNA genome of the **retrovirus**

What else does gp120 bind to?

human chemokine receptor

What facilitates the fusion of viral and host-cell memebranes?

gp41

What is the virus encoded heterodimer composed of?

gp120 and gp41

Which T cells are not infected by HIV?

CD8

Where do broadly neutralising antibodies bind to on a broad range of HIV variants?

highly conserved regions

Besides the CDR loops where else has broadly neutralising antibodies undergone different rounds of antigen-mediated somatic mutation and have acquired mutations?

framework regions

When do broadly neutralising antibodies emerge in someone with HIV?

after at least two years

What is the name of the process where successive episodes of stimulation generate high-affinity, strain-specific antibodies through multiple rounds?

affinity maturation

Why is having long CDR loops on broadly neutralising antibodies good?

enables them to penetrate the glycans that protect the viral spikes of **HIV**-1 and to gain more efficient access to gp120

What strain of HIV are elite neutralizers are unique in their ability to synthesize antibodies that bind and **neutralize?**

HIV-1

What copies the RNA genome into cDNA when a cell becomes infected with HIV?

reverse transcriptase

What are lentiviruses?

slow progressing diseases

What genes are common to all retroviruses?

gag, pol, and env

What are exogenous retroviruses?

infective retrovirus that originates outside the species being infected.

What are endogenous retroviruses?

retrovirus that has been integrated into the genome of a species

What is seroconversion?

phase of an infection when antibodies against the infecting agent are first detectable in the blood.

What is viremic controllers?

HIV-infected individuals who maintain a low viremia with 2000 copies or fewer of viral RNA per milliliter of blood, and maintain good health.

What carries proviruses?

infected T cells, dendritic cells and macrophages

What carries virons?

blood, semen, vaginal fluid, or mother’s milk

How do chimpanzees resist HIV?

chimpanzee CD4 does not bind the virus

Which HIV variant requires a low level CD4 on the surface?

Macrophage-tropic

Which HIV variant requires a high level CD4 on the surface?

Lymphocyte-tropic

Which cells are infected at the start of an infection?

macrophages and dendritic cells at site where virus enters body

What is the viral phenotype change to at a late stage of infection?

Lymphocyte-tropic

What transcription factor binds to promoters in the provirus?

NFκB

What does the tat protein do?

binds to a sequence in the LTR of the viral mRNA, known as the transcriptional activation region (TAR), where it prevents transcription from shutting off and thus increases the transcription of viral RNA

What does the rev protein do?

controls the supply of viral RNA to the cytoplasm and the extent to which that RNA is spliced

What stage to opportunistic infections become more frequent?

Before the symptomatic phase and a CD4 count falls 500 cells/μl

When is a patient diagnosed with AIDs?

CD4 T-cell counts fall below 200 cells/μl

What is the asymptomatic period which lasts 2-15 years?

asymptomatic period

What genetic basis for those who are able to resist infection?

mutated allele of the CCR5 gene, in which a 32-nucleotide deletion from the coding region leads to an altered reading frame, premature termination of translation, and a nonfunctional protein

What deletion variant only found in European origin?

CCR5-Δ32

What is CCR5 a receptor for?

chemokines CCL3, CCL4, and CCL5

What do people infected with HIV do to prevent the overt symptoms of disease?

adaptive immune response

What is involved in preventing the overt symptoms of disease?

TH1 and TH2 cells, B cells that make neutralizing antibodies, and cytotoxic CD8 T cells that kill virus-infected cells

What drug is given to HIV-infected pregnant women?

zidovudine, an inhibitor of the viral reverse transcriptase

What parasitic infections are those with HIV more susceptible?

Toxoplasma species

Cryptosporidium species

Leishmania species

Microsporidium species