Flashcards in Skildum- HIV Deck (33)
two copies of + ssRNA
Yes, gp120, gp41
What is the tropism for HIV?
CD4 T cells (also CD4 monocytes and macrophages)
What are the three enzymes that the virus particle contains?
What are the main genes in the HIV genome?
What does gag encode for?
What does pol encode for?
What does env encode for?
What are LTRs?
bind to host TFs (NFkB, Sp-1, TBP)
Integrase recognizes thses sites and cuts host genome here to insert viral genome
strong promoters act as NfkB regulated promoters
Here's a doosey.
describe the infection cycle
1. Protein at surface of viral particle interacts w/ protein of host cell
2. virus enters cell and uncoats
3. Genomic RNA is dumped into cytoplasm w/ RT, integrase and protease
4. RT copies genome into dsDNA
5. I ntegrase inserts dsDNA into host genome (provirus)
6. Once inserted you get expression of viral genes (turns on trxn and trln material to make viral particle and trxn of viral genome)
7. Unprocessed genomic RNA is released
8. Virus buds out through pm to infect other cells
What is the difference between spliced and unspliced RNA?
Early in infection--spliced
Splicing of genome> rev, nef, tat> machinery to make viruses (doesn't end up in particle)
Later in infection- unspliced
Unspliced RNA is translated to make:
1. structural and enzymatic proteins of viral particle
2. viral genome
What is the normal function of CD4 T cells in cellular immunity?
IL-2 response: Th1, activates CTLs (CD8+ T cells)
Fights off opportunistic infections
IL-4,5,6 response: Th2, activates B cells to become plasma cells
What is the consequence of losing CD4 T cells?
You can't fight off infections
What are common opportunistic infections?
Kaposi sarcoma virus (KSV, HHV-8)- almost exclusively found in immunocompromised
Cytomegalovirus (CMV, HHV-4)- Mono in person w/ normal immune system, in pt w/ advanced ageà systemic infection
Candida- yeast infection
How do you diagnose HIV?
ELISA confirmed by western blot
How do you monitor pts w/ HIV?
CD4 T cell enumeration by flow cytometry
PCR: viral RNA orDNA
What is the goal of therapy?
Reduce the level of circulating virus
-keep CD4 counts high
-lower viral load limiting ability to infect someone else
What are the side effects of NTRIs?
Fatal lactic acidosis w/ fatty liver (d/t inhibition of mitochondria)
What drugs are NTRIs?
Hypersensitivity rxn (esp in HLAB570 + pt)
Florinated analog of lamivudine
3TC cytosine analog
Analog of adenosine
Renal Side effects
What drugs are NNRTIs? What are common SEs?
drug interactions (cyp 450)
central fat accumulation
What drugs are protease inhibitors?
What are common SE of protease inhibitors?
Central Fat accumulation
Metbolized by and inhibit hepatic cyp3A4--> drug interactions
Inhibits HIV-1 aspartic protease
Blocks post-translational modificaiton of gag and gag pol genees
Competitive inhibitor of HIV protease>
Inhibits virus specific processing of gag-pol proteins>
preents formation of mature virirons
Competitive HIV protease inhibitor
High affinity for CYP3AA> many drug interactions