HIV Flashcards
What is HAART?
Highly active anti-retroviral therapy - combination of 3 drugs.
- 2x nucleoside reverse transcriptase inhibitors
- 1x “other” class of antiviral
What regulatory protein is required for HIV genome transcription?
Tat
How does regulatory Rev contribute to spreading of the virus?
Rev regulates viral expression of intact genome and transported to the cytoplasm without being spliced.
(Rev’s it up…!)
What is the host cellular defense that can prevent virus spread?
deoxycytidine deaminase, host protein that gets incorporated into virion and carried to new cell where it removes amines from the viral genome preventing its function.
What are two of HIV’s “restriction factors” that overcome cellular defenses?
Vif - induces degradation of cytidine deaminase preventing it from being transfered with the virion.
Vpu - inhibits host cell from tethering the released virions.
What co-receptor is required for M-trophic strains?
CCR5 Receptor, located on primary T-cells and Macrophages.
–Form that dominates in asymptomatic persons–
How does T-tropic HIV differ from M-trophic?
T-trophic is primarily present during the AIDs phase of the disease and is associated with progression of the disease.
Binds the CXCR4 co-receptor.
What kind of people have a very high resistance to infection with HIV?
Those with a CCR5 gene mutation - preventing expression of the receptor on the cell surface without any noticeable health changes.
–DRUG TARGET– binding CCR5 blocking virus access
What virus virulence factor inhibits Tetherin?
Vpu
What are the step in the fusion process?
First - binding of the CD4+ receptor, which causes conformational change exposing the co-receptor and fusion proteins.
Second - fusion proteins extend out from the virus complex binding to the membrane, unable to proceed until co-receptor is bound.
Third - Co-receptor CCR5 binds, fusion proteins “Snap” back onto virus complex completing the membrane fusino.
What kind of drug was produced to prevent membrane fusion?
A peptide that mimics the “snapback” region of the virus binding to the extended fusion proteins, preventing their function. -Fuzeon-
What location does virus infection/replication reside in the beginning of disease process?
Lymph Nodes, once high enough infection some spills into the blood since immune system prevents.
Why does infection localize to the lymph nodes?
Since HIV usually penetrates mucosal surfaces and the resident DC cells recognize the foreign antigen and binds it, bringing it to the lymph node to be present to T-cells.
–DC cells facilitate the infection–
Which trophism is most important for transferring of the virus?
M-Tropic, or R5
What are the common ways in which T-cells are killed in HIV?
Directly - lysis by HIV, merging with uninfected cell, apoptosis
Indirectly - CD 8+ cells destroy the CD4+ infected cells
What are the phases of an infection?
Acute Infection - steep increase in virus load, activates humoral and cytotoxic T-cell response.
- Virema is cleared by B/CD8 cells, but CD4 count continues to decline.
Late Stage - once CD4 count get too low, immune system failure - AIDS
What is a classic sign indicating HIV?
Infection by opportunistic organisms.
What are most common therapeutic targets?
- RT inhibitors
- Protease Inhibitor
- Fusion Inhibitor
- Entry Inhibitor
- Integrase inhibitor
Who should get screen for HIV?
Anyone between 13-64 age Pregnant patients IV drug users Commercial sex worker At least 1 new sexual partner since last screening
When do the first symptoms onset after exposure?
Symptoms first arise about 2-6 weeks after infection
What are the common acute infection symptoms?
Viral Syndrome - Fever, Myalgias, Weight loss, RASH, lympadenopathy, fatigue, oral ulcers
How can you diagnose HIV?
4-6 weeks after infection - ELISA Antibody testing
–after immune system mounts response - Cheap
Antigen Testing - p24 and HIV RNA - 10-14 days
Combined Antibody/Antigen - 3 weeks
What is the recommendation for HIV treatment?
After starting treatment, should never discontinue, even if viral load becomes undetected.
What is the goal of treatment?
To get viral load below levels of detection to prevent the chances of it spreading to others.
