HIV / AIDS

Question 1

What is the purpose of the gag gene?

Answer 1

Makes p24 = capsule for RNA strands.

Question 2

What is the purpose of the pol gene?

Answer 2

Makes reverse transcriptase = creates DNA from RNA

Question 3

What is the purpose of env gene?

Answer 3

Makes glycoproteins 41 and 120 “Take out the 1’s = 4/20 for pot);
Gp120 is the outer glycoprotein
Gp41 is the inner glycoprotein

Question 4

What is the transmission of HIV?

Answer 4

Sexual, vertical or blood transmission TORCHeS infection

Question 5

What cells does HIV infect?

Answer 5

Infects macrophages and Helper T-cells (CD4’s)

Question 6

What diseases or clinical features result from the initial HIV infection?

Answer 6

Lymphadenopathy, fever, diffuse LARGE B-cell lymphoma (via CCR5 co-receptor attachment)

Question 7

What is the clinical marker for progression of an HIV infection to AIDS?

Answer 7

As soon as CD4 count < 200, the disease has progressed to AIDS or a sudden steep decline in CD4+ cells. AIDS can also be diagnosed if above.

Question 8

Describe the mechanism by which HIV infects host cells.

Answer 8

HIV gains entry in CCR5 receptor in early stages or CXCR4 co-receptor in late stages.

Question 9

Describe how screening is done to clinically diagnose HIV infection.

Answer 9

Screen for antibodies first with ELISA test and confirm with a Western Blot performed via gel electrophoresis.

Question 10

What is the best way to test a neonate for suspected HIV infection?

Answer 10

HIV RNA and HIV DNA NAAT testing, since vertical transmission of the infected mother’s antibodies can confer a (+) result on ELISA/Western Blot. This evaluates the viral load itself, rather than antibodies.

Question 11

Describe the key drugs for anti-retroviral therapy.

Answer 11

1. Nucleotide Reverse Transcriptase Inhibitors (NRTI’s) = backbone, analog that halts further elongation. I.e.) Zidovudine for pregnant mothers;
2. NNRTIs = doesn’t incorporate into viral DNA, but stops elongation;
3. Protease inhibitors = cleave proteins for viral replication;
4. CCR5 inhibitor = Maraviroc

Question 12

What are the 4 ways to transmit HIV?

Answer 12

1. Sexual contacts
2. Blood/ transfusion products
3. IV drug use (dirty needles)
4. Perinatal infection during delivery (w/o prophylaxis)

Question 13

Briefly list and define the screening techniques for diagnosing HIV positivity.

Answer 13

1. ELISA assay - highly sensitive and specific; detects both ABs and p24 antigen (1 month window), follow up with Western Blot if positive;
2. PCR = picks up new infections effectively (4-7 day window), used sparingly in targeted situations

Question 14

What is the followup test for HIV positivity?

Answer 14

Western Blot of viral protein (confirmation test); viral load tests in developing countries

Question 15

What HIV binding interactions are known to prevent viral entry into the cell?

Answer 15

1. Strong (gp120) binding to CD4

2. gp120 binds CCR5 co-receptor = dual trophic binds monocytes

Question 16

Describe how T-cells are linked to an HIV infection.

Answer 16

HIV gene expression is linked to T-cells being infected or silent. Silent T-cells = Silent HIV

Question 17

Describe the role of HIV Tat.

Answer 17

Binds to TAR RNA at 5’ end of HIV RNAs. This activates viral txn via recruitment of of cell proteins.

Question 18

Describe the role of HIV Rev.

Answer 18

A HIV regulatory protein that prevents the splicing of RNAs and takes them out of the nucleus. Without Rev, all the RNAs get spliced to completion which is not good for the virus.

Question 19

Describe the purpose of HIV accessory proteins. Define the 3 examples (Nef, Vif, Vpu).

Answer 19

Proteins that interact with cellular proteins to promote infection and pathogenesis;
Nef = effector functions, produces AIDS-like symptoms
Vif = viral infectivity factor, blocks mutagenesis of HIV genome
Vpu = stimulates virus release from infected cell surface

Question 20

What is the purpose of VPU in HIV?

Answer 20

Counteracts against a cellular protein (Tetherin) that would prevent virus from budding off. Without VPU, viruses cannot bud off dying cells to infect others.

Question 21

What are the 1st cells to be infected initially by HIV?

Answer 21

Monocytic cells in the submucosa. CCR5-tropic strains predominate early.

Question 22

What determines HIV Tropism?

Answer 22

HIV gp120 amino acid sequence determine co-receptor binding preference. This is via CCR5 (determines tsm) and CXCR4 (T-t

Question 23

Define CCR5 binding

Answer 23

Associated with infection of primary activated CD4+ T cells and monocytes. Early transmission is linked to this.

Question 24

Define CXCR4 binding

Answer 24

Associated with infection of activated and immortal CD4+ T cells. Appears later in infection and replicates more rapidly.

Question 25

Describe what cells increase in number during an initial HIV infection.

Answer 25

CD8 cells pick up as part of the initial immune response against HIV, especially in lymph nodes

Question 26

Describe what occurs in the asymptomatic period of HIV infection.

Answer 26

Virus is cleared from the blood, BUT replication persists in the lymphoid tissues. CD4+ T-cells are still being destroyed = virological latency.

Question 27

Describe what occurs in the Long-term immune response to HIV.

Answer 27

Viral variability lowers the immune system’s effectiveness. Mutations in CTL epitopes and MHC-binding domains “blinds” the immune system to viruses. Virus outruns the immune system

Question 28

Define Viral variability.

Answer 28

This occurs each time a virus escape after the immune system tries to block it. Eventually, the immune system loses it’s effectiveness from mutations in CTL epitopes and MHC binding domains.

Question 29

Where is an important neutralzing domain in the HIV envelope encoded?

Answer 29

Within the variable region of the HIV SU (V3)

Question 30

Describe how CD4 and viral load can indicate HIV disease progression.

Answer 30

1. CD4 cell levels tell you where you are in the disease

2. HIV RNA predict where you are going

Question 31

Briefly summarize the pathogenesis of HIV infection.

Answer 31

1. Increased viral replication = more viral variation
2. Inc. viral variation = escape from immune response
3. Inc. resistance to drugs and implications of persistent viral reservoirs

Question 32

What population is the elite controllers of those who are HIV (+)?

Answer 32

A subset of long-term non-progressors that have undetectable amounts of virus in the blood for months to years WITHOUT THERAPY!

Question 33

What makes developing a vaccine for HIV difficult?

Answer 33

Genetic diversity in envelope variability protected by heavy glycosylation blocks ABs from binding.

Question 34

Name at least 3 problems to developing HIV vaccines.

Answer 34

1. Viral variability
2. Brief early window to block infection
3. Little ethical value behind vaccine trials when PrEP is available.

Question 35

List at least 2 promising approaches to HIV vaccines.

Answer 35

1. Broadly neutralizing antibodies may develop immune response.
2. Recombinant vaccines with gp120

Question 36

Describe the significance of PrEP.

Answer 36

Early initiation of PrEP may reduce the risk of HIV transmission to almost 100%.

Question 37

What HIV accessory protein binds nascent HIV transcripts and recruits protein kinase which up-regulates viral transcription?

Answer 37

Tat protein

Question 38

What change in the HIV virus marks the transition from the asymptomatic period to AIDS developing?

Answer 38

Macrophage-tropic virus is replaced by T-cell tropic virus. Receptor changes from CCR5 to CXCR4 (early to late-stage).

Question 39

What major advantage does PCR assays have over ELISA for diagnosing acute HIV infection?

Answer 39

PCR tests become positive more rapidly after infection (although more expensive).

Question 40

In a person with HIV infection, what is the best predictor for the patient’s future course of the disease? What of the current state?

Answer 40

1. Viral load in the peripheral blood

2. CD4+ T-cell count in peripheral blood