HIV Flashcards
How do you detect HIV?
Established infection: ELISA test, Western blot to confirm, or Rapid HIV to confirm
Acute infection: ELISA & Western may be negative, so check viral load with plasma HIV-1 RNA test (this is because viremia occurs before immune response occurs)
What is the structure of HIV?
2 copies of ssRNA
Icosahedral nucleocaspid
Lipid envelope
Remember that it has reverse transcriptase which changes the RNA to DNA, which integrates to host cell genome
What is included in the HIV genome?
Gag: internal structural proteins
Pol: major enzymes (reverse transcriptase, protease, integrase)
Env: envelope proteins
Also accessory proteins:
- *Tat** activates transcription
- *Rev** is a promoter
- *Nef** downregulates expression of CD4 and MHC1 on infected CD4 cell, so it escapes CD8 mediated killing
- *Vif** is required for dsDNA to be produced
- *Vpr** regulates nuclear import
- *Vpu** downregulates CD4 and MHC1/mediates HIV virion release
How does pathogenesis of HIV occur?
- Virus-dendritic cell interaction
- DC carries virus to lymph nodes (or virus infects T cells in the mucosa)
- viremia and viral dissemination, loss of CD4+ T lymphocytes from GALT
- Downregulation of virus replication by immune system by CD8 cells
- Viral set point is reached after 6 months & predicts disease progression
** viremia –> immune response which knocks down infection to a viral set point
Who should be tested for HIV?
Individuals at high risk based on their lifestyle
Individuals with symptoms compatible with HIV infection
What are the symptoms of acute HIV infection?
5-30 days after exposure, 50-90% of individuals are symptomatic
Flu like symptoms, aseptic meningitis, candidiasis, rash, weight loss, leukopenia, thrombocytopenia, elevated liver enzymes
GI associated lymphoid tissue depletion following acute infection –> “leaky gut” - bacterial translocation
Most symptoms clear after 14 days
Remember that viremia is highest during acute HIV and that this stage may be asymptomatic
What is the pathogenesis of established HIV infection?
Active viral replication is still going on: 10^9 virions are produced/destroyed each day; T1/2 of HIV in plasma is short!
Major reservoirs of infection exist outside blood compartment i.e. GALT, CNS, UG tract
You will develop quasispecies of viruses even if you’re only infected with one strain because it mutates and creates new strains
What is responsible for variability in course of HIV infection?
Strength of innate/adaptive immune response
Chemokine receptor status
HLA type of the individual
What are the different types of HIV progressors?
Depends on how long it takes for an individual to develop AIDS: typical is 8-10 years
Rapid progressors: within 2 years
Long term non progressors (LTNPs): maintain normal CD4 count and low viral load in absence of treatment for 10-15 years
Elite controllers: viral loads of less than 20 copies/ml in absence of retroviral therapy
What viral factors determine outcome of HIV infection?
Escape from immune response
Attenuation: not typical
Tropism: different starins
Subtypes
What is trim 5 alpha?
Disrupts caspid uncoating
Potential new therapeutic agent for HIV
What is Apobec 3G?
Human protein
Screws up reverse transcription
But HIV has Vif to counteract it
What is Tetherin?
Surface protein that tethers viruses together so they can’t become infectious
But HIV has Vpu which blocks tetherin’s activity
What protects the host from HIV infection?
Cell mediated immunity: CD8 cells eliminate virus infected cells & control viremia, T-helper response
Humoral immunity
Chemokine receptors
HLA
How do CD4+ cells die in HIV infection?
Apoptosis due to direct cytotoxic effect of HIV, lysis by CTL’s
Activation induced cell death in HIV uninfected cells due to release of proteins from neighborhing cells
