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IHO Week 6 > Skildum- HIV > Flashcards

Skildum- HIV Flashcards

1
Q

HIV classification:
genome
capsid
envelope

A

two copies of + ssRNA
icosahedral
Yes, gp120, gp41

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2
Q

What is the tropism for HIV?

A

CD4 T cells (also CD4 monocytes and macrophages)

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3
Q

What are the three enzymes that the virus particle contains?

A

Reverse transcriptase
Integrase
Protease

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4
Q

What are the main genes in the HIV genome?

A

gag
pol
env
LTR

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5
Q

What does gag encode for?

A

capsid proteins

p24

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6
Q

What does pol encode for?

A

RT
protease
integrase

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7
Q

What does env encode for?

A

envelope glycoproteins
gp120
gp41

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8
Q

What are LTRs?

A

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

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9
Q

Here’s a doosey.

describe the infection cycle

A
  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
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10
Q

What is the difference between spliced and unspliced RNA?

A

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

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11
Q

What is the normal function of CD4 T cells in cellular immunity?

A

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

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12
Q

What is the consequence of losing CD4 T cells?

A

You can’t fight off infections

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13
Q

What are common opportunistic infections?

A

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

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14
Q

How do you diagnose HIV?

A

ELISA confirmed by western blot

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15
Q

How do you monitor pts w/ HIV?

A

CD4 T cell enumeration by flow cytometry

PCR: viral RNA orDNA

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16
Q

What is the goal of therapy?

A

Reduce the level of circulating virus

  • keep CD4 counts high
  • lower viral load limiting ability to infect someone else
17
Q

What are the side effects of NTRIs?

A

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

Fat redistribution

18
Q

What drugs are NTRIs?

A 
Zidovudine 
AZT
Abacavir
Emtricitabine
Lamidvudine
Tenofovir
19
Q

Aidovudine, AZT

MOA
SE

A

NTRI

Deoxythymidine analog

granulocytopenia
anemia

20
Q

Abacavir

MOA
SE

A

NTRI

Guanine analog

Hypersensitivity rxn (esp in HLAB570 + pt)

21
Q

Emtricitabine

MOA

A

NTRI

Florinated analog of lamivudine

22
Q

Lamivudine

MOA

A

NTRI

3TC cytosine analog

23
Q

Tenofovir

MOA
SE

A

NTRI

Analog of adenosine

Renal Side effects

24
Q

What drugs are NNRTIs? What are common SEs?

A

Etravirine
Efavirenz

severe rashes
drug interactions (cyp 450)
central fat accumulation

25
Q

What drugs are protease inhibitors?

A

Atazanavir
Darunavir
Ritonavir

26
Q

What are common SE of protease inhibitors?

A

Central Fat accumulation

Metbolized by and inhibit hepatic cyp3A4–> drug interactions

27
Q

Atazanavir

MOA

A

Inhibits HIV-1 aspartic protease

Blocks post-translational modificaiton of gag and gag pol genees

28
Q

Darunavir

MOA

A

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

29
Q

Ritonavir

MOA

A

Competitive HIV protease inhibitor

High affinity for CYP3AA> many drug interactions

30
Q

What drugs are fusion entry inhibitors?

A

Enfuvirtide

Maraviroc

31
Q

Enfuvirtide

MOA
SE

A

Binds gp41 and prevents HIV fusion and entry

Local hypersensitivity
bacterial pneumonia

32
Q

Maraviroc

MOA
SE

A

CCR5 Antagonist- blocks co-receptor required for entry

pyrexia
rash
postural dizziness

33
Q

Raltegravir

MOA

A

Integrase strand transfer inhibitor

Pyrimidinone analog that bind integrase (enzyme essential to replication of HIV)

IHO Week 6 (14 decks)

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