Immunology Unit 11

HIV/AIDS

What is acquired immunodeficiency syndrome (AIDS)?

a chronic immune deficiency caused by HIV

What is reverse transcriptase?

• an enzyme found in RNA in the core of retroviruses

• converts RNA to DNA

• viruses that have this RNA are known as retroviruses

What are the two types of HIV that cause AIDS?

• HIV type 1

  • causes the vast amount of infections globally, split into 3 groups:

    • Group M (major) makes up 90% of all HIV 1 infections

    • Group O (outlier) is endemic to West Central African nations

    • Group N (neither) is found in Cameroon

• HIV type 2

  • prevalent in West Africa (very low in the US)

  • less virulent than type 1

• treatment is different for each type

List and describe the 2 main structures of the HIV

• envelope

  • double membrane

  • contains knob-like glycoproteins (gp120) with another glycoprotein on top (gp41)

• core

  • surrounded by structural proteins

  • contains single stranded RNA

  • also contains protease (p10), integrase (p32), and reverse transcriptase

What are the 3 predominant genes found in the virus’ genome?

• gag gene

  • encodes for viral core particles (protease and integrase)

• env gene

  • encodes for the envelope proteins p41 and p120

• pol gene

  • encodes for reverse transcriptase

What types of cells is HIV drawn to?

• mostly CD4 T lymphocytes (T helper cells)

  • CD4 acts as a receptor for gp120 to attach and enter the cell

• can also invade other CD4 cells: macrophages and monocytes

  • these cells can enable HIV 1 to enter the CNS

How does HIV invade CD4 host cells? (4 steps)

1. gp120 (envelope protein) binds to CD4 and the co-receptor CCR5 or CXCR4 on the host cell

   1. virus must bind to both to enter the cell

2. gp41 (envelope protein) undergoes a confirmational change and inserts itself into the T cell membrane

3. HIV and T cell membranes fuse

4. core contents inside the HIV enter the CD4 cell

Describe the 6 steps of HIV replication

1. reverse transcriptase transcribes viral RNA into DNA

2. using integrase, HIV inserts the new viral DNA into the host genome

3. transcription of the host DNA with the inserted viral DNA takes place

4. replication occurs: the virus uses the host cell’s machinery to make chains of HIV proteins

5. mature virions are produced and escape from the cell, looking to infect more CD4 cells

6. CD4 cells are eventually destroyed

How is HIV 1 and HIV 2 transmitted?

• HIV 1

  • cervicovaginal, penile, rectal, oral, percutaneous (skin puncture), intravenous, in utero, or breastfeeding routes

• HIV 2

  • primarily by heterosexual contact

80% of HIV 1 infected adults are infected through exposure to __________, while 20% are infected through the _______ route

mucosal surfaces containing the virus, percutaneous or IV

HIV can be transmitted as:

• the virus itself

• OR as a cell-associated HIV

Which 9 fluids has HIV 1 been isolated from?

blood, semen, vaginal secretions, saliva, tears, breastmilk, CSF, urine, and amniotic fluid

Which 4 fluids are known for transmitting HIV?

blood, semen, vaginal secretions, and breastmilk

What are the 5 stages of HIV (according to the CDC)?

• Stage 0

  • early stage, inferred from a negative or indeterminate test result within 6 months of a confirmed test

• Stages 1, 2, 3

  • based on CD4 lymph count

• Stage Unknown

• stage can change after diagnosis

Describe how HIV progresses

• Stage 0 can last months to years after initial infection

  • can be completely asymptomatic or exhibit mild, chronic lymphadenopathy

  • HIV 1 soon causes a progressive derangement of immune function

• 2 to 10 years after infection, virus replication can flare up again, and the infection enters the final stage

• 8 to 10 years can pass before AIDS finally develops

  • different manifestations based on the host

• end stage (stage 3)

  • CD4 lymph count is < 200 cells (normal is 500-1200)

  • neoplasms and opportunistic infections

How can infected CD4 cells destroy more CD4 cells?

• gp120 can break off of the virus and bind to CD4 receptors on uninfected cells

  • this stimulates the immune system to destroy these cells

• so not only can viral replication induce CD4 cell death, HIV can also cause the immune system to destroy its own cells

The normal ratio of CD4 T lymphocytes to CD8 lymphocytes is 2:1. What is the ratio in HIV/AIDS?

• 0.5:1

  • it is reversed

• normally, there are 65% CD4 cells and 35% CD8 cells in the body, in AIDS, it is reversed (more T regs)

What is syncytia?

when HIV infected cells and uninfected cells fuse together into giant, nonfunctional cells

List 10 opportunistic infections, and 2 neoplasms that are common in AIDS

• opportunistic infections/pathogens

  • P. jiroveci

  • Cytomegalovirus

  • Mycobacterium avium

  • Cryptococcus (fungal)

  • Toxoplasmosis

  • M. tuberculosis

  • Herpes Simplex Virus

  • Legionella

  • Histoplasma capsulatum

  • Cryptosporidiosis

• neoplasms

  • Kaposi sarcoma and malignant B-cell lymphoma

Which acute phase reactants are seen in HIV/AIDS?

alpha 1 antitrypsin and serum amyloid (seen before antibody appears)

What is seronegativity, and what is it in HIV/AIDS?

• seronegativity: the absence of specific antibodies for an antigen (virus, bacteria, RF, etc.), ABs are not created yet

• the first 6 to 12 weeks in HIV

antibodies for gp41 in patient plasma are detectable:

all throughout the infection

List 2 screening methods and 4 confirmatory tests for detecting HIV/AIDS

• screening tests

  • ELISA

  • rapid testing (fast but not sensitive)

• confirmatory tests

  • RNA detection nucleic acid amplification testing (NAAT)

  • western blot (detects proteins)

  • PCR

  • quantitative RNA assay

What 2 tests are used for monitoring HIV?

viral load testing and CD4 lymphocyte testing (flow cytometry for immune function)

What are the 7 treatments (not cures) for HIV/AIDS?

• nucleoside and non-nucleoside reverse transcriptase inhibitors

  • blocks reverse transcriptase; no replication occurs

• protease inhibitors

  • prevents protease from replicating

• fusion inhibitors

  • inhibits virus from fusing into CD4 cells

• entry inhibitors (CCR5 antagonist)

  • keeps the virus from binding to co-receptors on CD4 cells

• integrase strand transfer inhibitors

  • prevents HIV from integrating its genome into the host cell’s genome

• pre and postexposure prophylaxis