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Flashcards in Skildum- HIV Deck (33)
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1

HIV classification:
genome
capsid
envelope

two copies of + ssRNA
icosahedral
Yes, gp120, gp41

2

What is the tropism for HIV?

CD4 T cells (also CD4 monocytes and macrophages)

3

What are the three enzymes that the virus particle contains?

Reverse transcriptase
Integrase
Protease

4

What are the main genes in the HIV genome?

gag
pol
env
LTR

5

What does gag encode for?

capsid proteins
p24

6

What does pol encode for?

RT
protease
integrase

7

What does env encode for?

envelope glycoproteins
gp120
gp41

8

What are LTRs?

integration sites
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

9

Here's a doosey.

describe the infection cycle

1. Protein at surface of viral particle interacts w/ protein of host cell
Gp120:CD4
Gp41:CCR5/CXCR4
CSCR4: SDF-1
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

10

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

11

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
Parasitic infection

12

What is the consequence of losing CD4 T cells?

You can't fight off infections

13

What are common opportunistic infections?

Viral:
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

Fungal:
Candida- yeast infection

Protozoa:
Cryptococcus
Pneumocystis

14

How do you diagnose HIV?

ELISA confirmed by western blot

15

How do you monitor pts w/ HIV?

CD4 T cell enumeration by flow cytometry

PCR: viral RNA orDNA

16

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

17

What are the side effects of NTRIs?

Fatal lactic acidosis w/ fatty liver (d/t inhibition of mitochondria)

Fat redistribution

18

What drugs are NTRIs?

Zidovudine
AZT
Abacavir
Emtricitabine
Lamidvudine
Tenofovir

19

Aidovudine, AZT

MOA
SE

NTRI

Deoxythymidine analog

granulocytopenia
anemia

20

Abacavir

MOA
SE

NTRI

Guanine analog

Hypersensitivity rxn (esp in HLAB570 + pt)

21

Emtricitabine

MOA

NTRI

Florinated analog of lamivudine

22

Lamivudine

MOA

NTRI

3TC cytosine analog

23

Tenofovir

MOA
SE

NTRI

Analog of adenosine

Renal Side effects

24

What drugs are NNRTIs? What are common SEs?

Etravirine
Efavirenz

severe rashes
drug interactions (cyp 450)
central fat accumulation

25

What drugs are protease inhibitors?

Atazanavir
Darunavir
Ritonavir

26

What are common SE of protease inhibitors?

Central Fat accumulation

Metbolized by and inhibit hepatic cyp3A4--> drug interactions

27

Atazanavir

MOA

Inhibits HIV-1 aspartic protease

Blocks post-translational modificaiton of gag and gag pol genees

28

Darunavir

MOA

Competitive inhibitor of HIV protease>
Inhibits virus specific processing of gag-pol proteins>
preents formation of mature virirons

29

Ritonavir

MOA

Competitive HIV protease inhibitor

High affinity for CYP3AA> many drug interactions

30

What drugs are fusion entry inhibitors?

Enfuvirtide
Maraviroc