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How does HIV target and bind to the CD4+ T-cells
HIV has surface proteins that are capable of binding to CD4 along with coreceptors CCR5 or CXCR4 to form a trimolecular complex
→ this allows for fusion of the viral membrane to the host cell membrane
What is the purpose of reverse transcriptase? How can this be targeted?
Viral RNA needs to be converted into DNA in order to be incorporated into the genome of host cells for viruses like HIV. Done via reverse transcriptase
→ can either mimic RNA in order to block the active site of the reverse transcriptase
→ allosteric inhibition
What is Integrase?
Integrase is required for viral DNA, created from reverse transcriptase, to be input into the host genome
→ used by HIV In order to insert its genetic material into the host cell genome
What are the steps of HIV pathogenesis? (5)
HIV enters into the cell by attaching to CD4+ and coreceptors CCR5 or CXCR4
→ viral RNA enters and is reverse transcribed into DNA by reverse transcriptase
→ viral DNA is then inserted into the host genome via integrase
→ viral DNA can remain inert in the genome or is transcribed actively into viral mRNA which can be made into polyproteins Gag, Env, and Pol
→ Gag helps assemble the virus and is budded off from the host cell using a protease
What are the phases of HIV when comparing CD4+ T-cell count and viral number
HIV Phases
1) Single HIV particle makes it across the particle and leads to rapid proliferation leading to a rapid decrease in CD4+ T-cell
→ especially seen in the gut
2) HIV will then drop in count and then plateau in count instead of disappearing. This is because HIV is a really shitty replicator and makes different mutants that are capable of dodging our immune system
→ HIV count will typically drop through the action of CD8+ T-cells first (cellular immune response)
3) Clinical Latency
→ CD4+ T-cell will fluctuate and slowly atrophies down where after a certain point the viral load will begin to increase again
→ Collapse in CD4+ T-cell population leading to AIDS
What are the signs and symptoms of a primary HIV infection?
40-90 percent of patients will be symptomatic
→ mononucleosis-like illness with non-specific symptoms like fever, rash, or fatigue
How would you test for HIV?
Two ways: Antigen testing or Antibody testing
1) Antigen testing - immediate
→ HIV Antigen p24
→ HIV RNA
2) Antibody - delayed
→ IgM, IgG
What is the difference between 3rd Generation and 4th Generation Immunoassay? What is the best test?
3rd Generation Assay provides an antigen in order to test for the presence of IgM or IgG
→ shows up around 4 weeks
4th Generation Assay provides an antigen as well as a p24 antibody in order to test for the presence of IgM, IgG, and p24 in order to allow for earlier testing
→ shows up around 3 weeks following infection
→ first line test
By far the best test is checking for viral load which checks for RNA nucleic acid
→ definitive test when actively considering HIV
What is the highest risk activity for acute HIV transmission?
Receptive anal sex
Receptive vaginal sex, Insertive anal sex, Insertive vaginal sex
→ generally around the same, but in order from greatest to least risk
Oral sex
What is HIV Latency?
The virus becomes metabolically low active state following incorporation into the genome, remaining in the genome permanently
→ establishes latency permanently because of long-lived memory cells
Why do we use multiple agents to target HIV infection?
1 antiviral agent allow is insufficient to sustain viral suppression
→ using only one will select for only a single dominant mutant, allowing the other mutant strains of virus variants to still exist - HIV is too prone to rapid change
→ by using two we can stop and box in HIV mutation preventing spread, antiretroviral drugs will suppress HIV replication to undetectable levels
What is Immune Reconstitution Inflammatory Syndrome (IRIS)? What can cause it
After taking antiretroviral therapy/drugs their decreased CD4+ T-cell count will rapidly increase causing the immune system to rapidly turn on
→ causes massive inflammatory response associated with secondary infections from a depressed immune system waking back up
Most common associated pathogen with IRIS is
→ Mycobacterium avium complex (MAC)
What is the rate of HIV transmission to a HIV positive partner that is treated to a negative partner
virtually zero
→ there has been zero recorded cases of linked-transmission
How can HIV cause cancer?
Because there is a constantly present viral load, even in a latent or treated patient, there is a slightly elevated degree of activation of our immune system → leads to increased risk of malignancies
At what point does advanced AIDS show up?
When the CD4+ T-cell count drops below 200 - associated with a increased relative risk of opportunistic infections and AIDS symptoms
How is CMV associated with AIDS
Cytomegalovirus can cause opportunistic infections in patients with AIDS
→ patients will present with blurring or loss of central vision, resulting in a “scrambled eggs with ketchup” on the retina
What can cause multiple lesions of the brain leading to stroke in patients with AIDS?
Toxoplasmosis
What can JC Virus cause in an AIDS infection
JC virus in AIDS patients can cause Progressive Multifocal Leukoencephalopathy
→ present with weakness and will have MRI findings of brain lesions with no atrophy
What can Mycobacterium Avium cause in AIDS patients?
Mycobacterium Avium infections in advanced AIDS can cause general symptoms of fever and wasting
→ interstitial infiltrates
What can Cryptococcus cause in an AIDS patient?
Cryptococcal Meningitis
→ causes fever, fatigue, headaches
