HIV / AIDS Flashcards
What is the purpose of the gag gene?
Makes p24 = capsule for RNA strands.
What is the purpose of the pol gene?
Makes reverse transcriptase = creates DNA from RNA
What is the purpose of env gene?
Makes glycoproteins 41 and 120 “Take out the 1’s = 4/20 for pot);
Gp120 is the outer glycoprotein
Gp41 is the inner glycoprotein
What is the transmission of HIV?
Sexual, vertical or blood transmission TORCHeS infection
What cells does HIV infect?
Infects macrophages and Helper T-cells (CD4’s)
What diseases or clinical features result from the initial HIV infection?
Lymphadenopathy, fever, diffuse LARGE B-cell lymphoma (via CCR5 co-receptor attachment)
What is the clinical marker for progression of an HIV infection to AIDS?
As soon as CD4 count < 200, the disease has progressed to AIDS or a sudden steep decline in CD4+ cells. AIDS can also be diagnosed if above.
Describe the mechanism by which HIV infects host cells.
HIV gains entry in CCR5 receptor in early stages or CXCR4 co-receptor in late stages.
Describe how screening is done to clinically diagnose HIV infection.
Screen for antibodies first with ELISA test and confirm with a Western Blot performed via gel electrophoresis.
What is the best way to test a neonate for suspected HIV infection?
HIV RNA and HIV DNA NAAT testing, since vertical transmission of the infected mother’s antibodies can confer a (+) result on ELISA/Western Blot. This evaluates the viral load itself, rather than antibodies.
Describe the key drugs for anti-retroviral therapy.
- Nucleotide Reverse Transcriptase Inhibitors (NRTI’s) = backbone, analog that halts further elongation. I.e.) Zidovudine for pregnant mothers;
- NNRTIs = doesn’t incorporate into viral DNA, but stops elongation;
- Protease inhibitors = cleave proteins for viral replication;
- CCR5 inhibitor = Maraviroc
What are the 4 ways to transmit HIV?
- Sexual contacts
- Blood/ transfusion products
- IV drug use (dirty needles)
- Perinatal infection during delivery (w/o prophylaxis)
Briefly list and define the screening techniques for diagnosing HIV positivity.
- ELISA assay - highly sensitive and specific; detects both ABs and p24 antigen (1 month window), follow up with Western Blot if positive;
- PCR = picks up new infections effectively (4-7 day window), used sparingly in targeted situations
What is the followup test for HIV positivity?
Western Blot of viral protein (confirmation test); viral load tests in developing countries
What HIV binding interactions are known to prevent viral entry into the cell?
- Strong (gp120) binding to CD4
2. gp120 binds CCR5 co-receptor = dual trophic binds monocytes
Describe how T-cells are linked to an HIV infection.
HIV gene expression is linked to T-cells being infected or silent. Silent T-cells = Silent HIV
Describe the role of HIV Tat.
Binds to TAR RNA at 5’ end of HIV RNAs. This activates viral txn via recruitment of of cell proteins.
Describe the role of HIV Rev.
A HIV regulatory protein that prevents the splicing of RNAs and takes them out of the nucleus. Without Rev, all the RNAs get spliced to completion which is not good for the virus.
Describe the purpose of HIV accessory proteins. Define the 3 examples (Nef, Vif, Vpu).
Proteins that interact with cellular proteins to promote infection and pathogenesis;
Nef = effector functions, produces AIDS-like symptoms
Vif = viral infectivity factor, blocks mutagenesis of HIV genome
Vpu = stimulates virus release from infected cell surface
What is the purpose of VPU in HIV?
Counteracts against a cellular protein (Tetherin) that would prevent virus from budding off. Without VPU, viruses cannot bud off dying cells to infect others.
What are the 1st cells to be infected initially by HIV?
Monocytic cells in the submucosa. CCR5-tropic strains predominate early.
What determines HIV Tropism?
HIV gp120 amino acid sequence determine co-receptor binding preference. This is via CCR5 (determines tsm) and CXCR4 (T-t
Define CCR5 binding
Associated with infection of primary activated CD4+ T cells and monocytes. Early transmission is linked to this.
Define CXCR4 binding
Associated with infection of activated and immortal CD4+ T cells. Appears later in infection and replicates more rapidly.
