Med Micro 9 - HIV:AIDS

Question 1

What would happen if an new unknown disease showed up?

Answer 1

News and media spread; healthmap/epidemiology data quick; international effort, sharing info, lots of funding; isolate virus, sequence genome;

Question 2

HIV general characteristics

Answer 2

Enveloped, positive ssRNA virus, Retroviridae. Type 1: US and Europe; Type 2 is only really found in west Africa

Question 3

What is a viral capsid?

Answer 3

the protein coat or shell of a virus particle, surrounding the nucleic acid or nucleoprotein core.

Question 4

Why acquired immunodeficiency diseases? (not syndrome)

Answer 4

Older people: thymus degrades with age, increases viral diseases and cancer; max age for attenuated vaccine. Severe stress: suppress cell-mediated immunity from excess corticosteroids (toxic to T cells)

Question 5

Thymus

Answer 5

Best up to about 20. Needed for maturation of T cells.

Question 6

Definition of AIDS

Answer 6

presence of opportunistic or rare infections associated with the presence of human immunodeficiency virus (HIV)

Question 7

HIV viral infection

Answer 7

Two subtypes can infect the same person and generate a new hybrid (CRF). Groups M, N, O, P. Sub groups of M: A-K + circulating recombinant forms

Question 8

Why is virus characterized as a retrovirus?

Answer 8

Uses DNA instead of its own RNA genome

Question 9

Clearly HIV has a very long incubation period. Why?

Answer 9

it inserts its DNA into the cells, but does not replicating, so no viruses are being generated right away. The long incubation period is beneficial, because it allows for the virus to live for a long time and to spread easier using the asymptomatic hosts.

Question 10

Use the info you know to explain the long incubation period

Answer 10

Hosts defenses, # of infecting microbes, nutrient availability, site of infection, nature of the microorganism, the life cycle, the rate of growth (what is the doubling time).

Question 11

Unlike many +ssRNA viruses, retroviruses do not use their genome as mRNA directly. Their +RNA is transcribed into the DNA by reverse transcriptase. What advantages do retroviruses gain by using reverse transcriptase?

Answer 11

Causes a ton of error. More variation in the HIV virus in one person than all the variation in influenza in the 20th century. Others?

Question 12

What cells does HIV target?

Answer 12

Th cells; monocytes and macrophages; smooth muscle (like arterial walls); dendritic cells. To note is macrophages secrete molecules to attract T cells.

Question 13

Structure of HIV

Answer 13

Glycoproteins gp120 (attachment) and gp41 (fusion). Both vary their antigens.

Question 14

Entry of HIV

Answer 14

gp120 binds to CD4. Complex binds to CCR5 or CXCR4. gp41 contacts membrane, fusion. gp41 stays on surface, causes syncytium (up to 500 cells clump)

Question 15

How does syncytium kill cells?

Answer 15

Cells clump together and then fuse. Signal for mitosis, fails due to too many poles and chromosomes, apoptosis. Causes mitotic failure during mitosis when the nuclear envelope breaks down

Question 16

Reverse transcriptase process

Answer 16

uses RNA as template for a -ssDNA, then degrades the RNA, and then makes dsDNA

Question 17

How do T cells die during HIV infection?

Answer 17

Reverse transcription in most of them doesn’t work well, incomplete DNA intermediates accumulate and trigger the cells to apoptosis. Drugs that block entry of virus or stop RT prevent it, drugs for later parts of cycle did not. Die, release cytokines, more get infected and inflammation

Question 18

Why are people infected with genital Herpes more at risk for HIV?

Answer 18

Immune system already in the area of the infection taking care of herpes, specifically the CD4 cells in that area were much higher, so they were more prone to HIV infection, as HIV is a sexually transmittable disease.

Question 19

Pathogenesis of AIDS

Answer 19

Stage 1: Acute Infection, virus increases, fever, fatigue, weight loss, T cell count drops. Stage 2: antibodies produced, body destroys ~billion virions each day but virus and Tc cells kill approx. million CD4 cells. Integrated virus continues to replicate, virions released into blood, no symptoms. Stage 3: cannot replenish T cells, Th cell number decreases, function lost, Ab count drops. Stage 4: virus increases, opportunistic infections. Stage 5: death occurs.

Question 20

Treatment?

Answer 20

HAART - highly active antiretroviral therapy. Nucleotide analogs, protease inhibitors, reverse transcriptase inhibitors. Expensive but effective. (video: fusion and integrase inhibitors too)

Question 21

Some stats on AIDS

Answer 21

over 33M have it. 25M have died from it. 1% of active adults have it. For every 2 people treated, 5 are infected. 65k have AIDS in Canada

Question 22

Why might a syncytium provide advantage to HIV?

Answer 22

Increases route of infection; virus hides in cells.

Question 23

What do cells infected with HIV die of?

Answer 23

Nutrient deprivation; reverse transcriptase errors leading to apoptosis; interferons (varies b/w viruses); immune response - Tc cells; syncytium

Question 24

With respect to pathogenesis of AIDS, give a detailed description of why we obtain the profile seen from Stage 1 to 2 for the HIV genome,CD4 cells and anti HIV Ab

Answer 24

Virus starts replicating, so Th cells die, Immune system responds to infection by producing Ab, so the virus level drops.

Question 25

Given that 1st exposure to HIV and subsequent ones stimulate the humoral and cellular immune response, why do anti-HIV Ab mirror a decrease in the number of CD4 cells in the blood?

Answer 25

Decrease T dependent humoral immune response so less Ab produced. No memory due to HIV diversity etc

Question 26

What mechanisms exist for generation of diversity in HIV? Discuss

Answer 26

Reverse transcriptase makes many errors. Different subtypes combine

Question 27

Be clear on the word “pathogenesis”

Answer 27

The steps in the development of the disease. Namely, entry, integration, killing and depletion of Th cells, opportunistic infections cannot be cleared. Th cell destruction is directly related to the course of AIDS