Lecture 20

Question 1

What is HIV?

Answer 1

human immunodeficiency virus

Question 2

What does HIV attack?

Answer 2

immune system
- CD4 (t-helper) cells

Question 3

What does the CD in CD4 mean?

Answer 3

clusters of differentiation

Question 4

How does CD4+ work?

Answer 4

• cytokine signaling with B cells
• interacts directly with antigens
• bind MHC class II molecules on B cells and APCs
• T-helper secretes costimulatory molecule

Question 5

What do T-helper cells produce?

Answer 5

cytokines into
-> T-helper 1 cells
-> T-helper 2 cells
-> T-helper 17 cells
-> memory cells

Question 6

What do T-helper 17 cells produce? What does it contribute to?

Answer 6

IL-17
- contributes to inflammation

Question 7

What do T-helper 1 cells produce? What does it do?

Answer 7

IFN-gamma
- activates macrophages
- enhances complement
- stimulate antibody production that promotes phagocytosis

Question 8

What do T-helper 2 cells release? What does it do?

Answer 8

IL-4 cytokine
- activates B cells to produce IgE
- activates eosinophils

Question 9

How are TH1 cells involved in HIV/AIDS?

Answer 9

• cell-mediated immunity
• activation of cytotoxic T cells and macrophages
• HIV leads to depletion of CD4+ TH1 cells, weakening the immune system’s ability to combat intracellular pathogens

Question 10

How are TH2 cells related to HIV/AIDS?

Answer 10

• associated with humoral immunity
• helps B cells produce antibodies
• balance between TH1 and TH2 is disrupted in HIV (TH2 more dominant) = contributes to reduced cell-mediated immunity

Question 11

How are TH17 cells related to HIV?

Answer 11

• mucosal immunity (defending against bacterial and fungal infections at epithelial barriers)
• HIV can impair TH17 cells (weakening of mucosal defenses and gut barrier integrity) = systemic inflammation and microbial translocation

Question 12

How are memory cells related to HIV?

Answer 12

• HIV establishes reservoirs in memory CD4+ T cells (latent virus)
• hard to eradicate virus entirely
• memory cells harbor latent HIV and can reactivate causing ongoing infection

Question 13

What is the structure of HIV?

Answer 13

• genus: lentivirus
• retrovirus (reverse transcription)
• 2 identical + stranded RNA genome molecules
• phospholipid envelope
• gp120 glycoprotein spikes
• capsid

Question 14

How does HIV infect the body?

Answer 14

• spread by dendritic cells and carried to the lymphoid organs
• contacts activated T cells
• gp120 combines with CD4+ receptor and CCR5 or CXCR4 coreceptors
• CD4 molecules are carried on Th cells, macrophages, and dendritic cells
• virus fuses and enters into the cell.

Question 15

How does HIV work inside the cell?

Answer 15

• viral RNA is transcribed into DNA using reverse transcriptase
• DNA is integrated into the host’s chromosomal DNA
• virus undergoes rapid antigenic changes and a high rate of mutation

Question 16

What is an active infection?

Answer 16

new viruses bud from the host cells

Question 17

What is a latent infection?

Answer 17

DNA is hidden in the chromosome as a provirus
- some become memory T cells that serve as the reservoir for HIV

Question 18

What are the characteristics of HIV-1?

Answer 18

• related to viruses that infect chimpanzees and gorillas
• 99% of cases
• group M (majority) accounts for 90%

Question 19

What are the characteristics of HIV-2?

Answer 19

• not often encountered outside of West Africa
• less pathogenic than HIV-1
• longer asymptomatic period with lower viral load and mortality rate than HIV-1

Question 20

What suppresses viral numbers?

Answer 20

cytotoxic T lymphocytes (CTLs)

Question 21

How is HIV transmitted?

Answer 21

• can survive 6 hours outside a cell and 1.5 days inside
• sexual contact
• breast milk
• transplacental infection of a fetus
• blood-contaminated needles
• organ transplants
• artificial insemination
• blood transfusion
• anal-receptive intercourse

Question 22

What are the phases of HIV infection?

Answer 22

Phase 1: asymptomatic or lymphadenopathy
Phase 2: CD4+ cells decline steadily (only a few infected cells release the virus)
Phase 3: AIDS develops, CD4+ is below 200 cells/microliter

Question 23

Who are long-term survivors of HIV exposure?

Answer 23

• low viral load
• effective CTLs

Question 24

What are the symptoms of HIV infection?

Answer 24

Acute stage: flu-like symptoms, high viral load
Chronic stage: asymptomatic or mild symptoms, virus continues to replicate
AIDS: severe immune system damage, opportunistic infections occur

Question 25

How can HIV be diagnosed?

Answer 25

• seroconversion: period of time between infection and the appearance of antibodies (takes 3 months)
• ELISA
• Western blotting or APTIMA (RNA test)
• Plasma Viral Load (PVL): determined by PCR or nucleic acid hybridization

Question 26

What are some challenges with developing HIV vaccines?

Answer 26

• no model of natural immunity to mimic
• lack of research animal
• lack of understanding of the mechanisms of retroviruses
• high mutation rate, leading to resistant strains

Question 27

What should an ideal vaccine do?

Answer 27

• induce immunity before reservoirs of latent virus are established
• stimulate production of CTLs
• be affordable

Question 28

What are AIDS?

Answer 28

Acquired Immunodeficiency Syndrome

Question 29

What is the origin of AIDS?

Answer 29

• HIV crossed over into the human populations in west and central Africa from chimpanzees
• spread throughout Africa as a result of urbanization and increased sexual promiscuity
• first known sample was from Kinshasa, DRC, in 1920

Question 30

What is the most common mode of HIV transmission?

Answer 30

heterosexual transmission
- 1/3 of cases in Eastern Europe and Central and Southeast Asia are from injected drugs

Question 31

How does HIV progress to AIDS?

Answer 31

1) HIV attacks and infects CD4+ T cells
2) HIV multiplies rapidly, destroying CD4+ cells over time
3) CD4+ counts drop = immune system becomes less able to fight infections
4) CD4+ levels fall below 200 cells/microliter = AIDS

Question 32

How can AIDS be prevented?

Answer 32

• biomedical interventions (condoms, HIV testing, needle programs)
• behavioral intervention (sex education, safe infant feeding programs, counseling)
• structural interventions (making changes in social, economic, political, and environmental factors to reduce vulnerability to HIV)

Question 33

How can AIDS be treated?

Answer 33

• Highly active antiretroviral therapy (HAART): combinations of drugs to minimize survival of resistant strains
• fusion/cell entry inhibitors: targets gp41 region of the viral envelope that prevents fusion of the virus with the cell
  = enfuvirtide and maraviroc
• Reverse transcriptase inhibitors
  = NRTIs (tenofovir and emtricitabine)
  = NNRTIs (efavirenz)
• integrase inhibitors: inhibits HIV integrase that integrates cDNA into the host chromosome
  = Raltegravir, dolutegravir, elvitegravir
• protease inhibitors: inhibit proteases that cleave viral precursor proteins into structural and functional proteins
  = Atazanavir, indinavir, and saquinavir
• maturation inhibitors: stop HIV from becoming infectious by blocking the final step in the virus’ replication process, where the Gag protein is processed