Immunologic Disease-HIV (2/18, Nguyen)

Question 1

What is at the core of an HIV-1 virion?

Answer 1

p24, the capsid protein, surrounds: 
Genomic RNA (2 copies)
Viral Enzymes (reverse transcriptase, etc)

Question 2

What surrounds the core of an HIV-1 virion?

Answer 2

p17 matrix protein

–lies beneath the virion envelope

Question 3

What is the virion envelope studded by?

Answer 3

gp41 and gp120

Question 4

What is the screening test for HIV?

Answer 4

ELISA

–several other diseases may provide a false positive (Lyme, syphilis, lupus)

Question 5

How are the results of the ELISA test confirmed?

Answer 5

Western Blot test - test for HIV proteins

A positive test = bands of p24, p33, gp41, gp120

Question 6

What host cells does HIV target?

Answer 6

CD4+ Helper T-cells

Macrophages/dendritic cells

Question 7

How does the HIV virus target CD4+ Helper T-cells and Macrophages?

Answer 7

HIV uses gp120 to bind to CD4+

gp120 has a site for the co-receptors CCR5 (macrophages) and CXCR4 (T-cells)

Question 8

Which HIV strains use which co-receptors?

Answer 8

HIV strain R5 uses CCR5 co-receptors

HIV strain X4 uses CXCR4 co-receptors

Question 9

Which strain infects the most cells?

Answer 9

Initially, 90% of the virus is transmitted by strain R5

Later in the progression of the disease, strain X4 accumulates and results in the rapid depletion of T-cells.

Question 10

How does the HIV genome enter the cell cytoplasm?

Answer 10

gp41!

On gp120 (the protein used by HIV to bind to CD4+), gp41 is a protein non-covalently attached.

gp41 allows a conformational change so that viral fusion takes place and the HIV genome is inserted into the host cell.

Question 11

How is viral genome replicated?

Answer 11

via reverse transcription to form cDNA

–May remain non-transcribed for months or years = latent phase

–May be transcribed immediately to form viral particles = productive infection

Question 12

What takes place during the acute phase of HIV?

Answer 12

3-6 weeks after infection, experience flu-like symptoms of sore throat, fever, rash

High viremia = seedling of the peripheral lymphoid tissues and reduced CD4+ T-cells

Towards the end of the acute phase, viremia ends and T-cell levels return to normal

Question 13

What takes place during the chronic phase of HIV?

Answer 13

Asymptomatic
Containment of the virus, though it is still replicating
HIV lacks a true microbiologic latency, but this is close.

Question 14

What takes place during the crisis phase of HIV?

Answer 14

Breakdown of host defenses
<500 cells/microliter = escalation of viral replication
Susceptible to opportunistic diseases

Question 15

What qualifies as AIDS?

Answer 15

< 200 cells/microliter
Without treatment, HIV becomes AIDS in 7-10 years

• -BUT, there are rapid progressors (< 2-3 yrs)
• -Non-progressors are asymptomatic (>10 years)

Question 16

What are the overall effects of HIV on lymphocytes?

Answer 16

1. Inversion of CD4:CD8 ratio in peripheral blood

2. defects in T-cell function

Question 17

What are the overall effects of HIV on macrophages?

Answer 17

1. HIV infected macrophages are in tissues, not the peripheral blood. Found in brain and lungs.
2. Infected macrophages have intraceulluar vacuoles which harbor the virus particles
3. Macrophages serve as factories and transport for HIV

Question 18

In the Central Nervous System, which cells are primarily infected with HIV?

Answer 18

Macrophages and microglia

Brain HIV strains are the R5 strain

Question 19

What are the neurological symptoms of HIV caused by?

Answer 19

Symptoms are caused by the viral products and soluble factors (cytokines) produced by the macrophages and microglia.

Note that neurons are NOT infected.

Question 20

What is the most common neoplasm in AIDS patients?

Answer 20

Kaposi sarcoma!

Multicentric and aggressive

Question 21

What virus has been found in conjunction with almost all Kaposi sarcomas?

Answer 21

Human Herpes Virus - 8 (HHV-8)