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IHO Week 6 > HIV/AIDS - Skildum > Flashcards

HIV/AIDS - Skildum Flashcards

1
Q

What is the most likely cell to transmit the infection (HIV)?

A

Macrophages

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2
Q

What is the genome of HIV?

A

Two copies of positive polarity RNA

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3
Q

What is the capsid symmetry of HIV?

A

Icosahedral

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4
Q

Does HIV have an envelope?

A

YES; includes p120 and p41 - why you need body fluids to transmit

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5
Q

What is the tropism of HIV?

A

CD4+ T cells (also CD4+ monocytes, macrophages)

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6
Q

Where are the proteins gp41 and gp120?

A

gp41 is bound to the envelope of HIV

gp120 is bound to the outside on top of gp41

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7
Q

What three enzymes does the HIV virus carry (KNOW FOR EXAM!!)?

A
  1. Reverse transcriptase
  2. Integrase
  3. Protease
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8
Q

What is important to know about the HIV-1 genome?

A
  • It is small and compact, with genes encoded on multiple overlapping reading frames
  • Less than 10,000 bp
  • Multiple proteins are produced from small number of genes
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9
Q

What does gag gene encode for (EXAM)?

A

Capsid proteins (p24 et. al.)

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10
Q

What does the pol gene encode for (EXAM)?

A

Encodes reverse transcriptase, protease and integrase

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11
Q

What does the Env gene encode for (EXAM)?

A

Envelope glycoproteins gp120 and gp41

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12
Q

What are LTRs (long tandem repeats) on HIV genome (EXAM)?

A

LTRs allow viral genome to integrate into host genome.
They also serve as binding sites to NF-KB.
[Integration sites; bind host transcription factors NF-kB, Sp1, TBP]

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13
Q

How does the viral genome of HIV integrate into DNA of cell?

A

Each ssRNA genome is bound to a primer that is a transfer RNA - this allows reverse transcription to start immediately upon infection

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14
Q

What happens first in the viral life cycle of HIV?

A
  1. First CXCR4 (CD4+ Cell) binds stromal derived factor-1
    CD4+ Target cells are infected by the virus
    CD120 binds to CD4 & this contact initiates another contact between the chemokine receptor and something –> all of these interactions allow the virus to inject itself into the cell
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15
Q

What can mediate how fast someone will progress in the infection?

A

Stromal derived factor-1 (SDF-1). It binds CXCR4.
-A polymorphism in the 3’UTR of SDF-1 may be associated with resistance to HIV-1 infection; effect on disease progression is less clear

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16
Q

What does stream derived factor-1 normally do?

A

Normally function to bind CXCR4 on lymphocytes and direct their homing to tissues.

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17
Q

What protein on HIV-1 infected T cells (provirus) binds to CXCR4? What does this cause?

A

Env proteins.
Binding of env to CXCR4 induces autophagy. This is a major cause of CD4+ T cell loss/disease progression in HIV-1 infection.

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18
Q

What are the initial steps of HIV infection that lead to viral DNA being integrated into T cell DNA?

A
  1. gp120 and gp41 interact with CD4 and chemokine receptors on cell surface
  2. This causes viral envelope to go into the cell/fusion
  3. ssRNA genome is then converted to DNA - Reverse transcriptase copies RNA genome into ssDNA
  4. Second polymerase step that doubles the ssDNA genome
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19
Q

What are the seven steps in the HIV-1 infection cycle?

A
  1. Binding of HIV-1 envelope glycoproteins to host cell receptors
  2. Envelope fusion with plasma membrane
  3. Reverse transcription to dsDNA
  4. Integration
  5. Expression of viral genes to make viral proteins & viral genomes
  6. Proteolytic processing of viral proteins (Env, Gag, Pol)
  7. Assembly of viral particles & budding from host cell
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20
Q

What does RNA Polymerase II do?

A

Changes the integrated proviral DNA in the nucleus into genomic RNA

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21
Q

What happens with an IL-2 response?

A

(IL-2 comes from CD4 - Th1 cells): It activates CTLs (CD8+ T cells)

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22
Q

What happens with an IL-4, 5, 6 response?

A

(IL-4, 5, 6 comes from CD4 - Th2 cells): It activates B cells to become plasma cells

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23
Q

What viral opportunistic infections are associated with HIV-1?

A
  • Kaposi sarcoma virus (KSV, HHV-8)

- Cytomegalovirus (CMV, HHV-5)

24
Q

What fungal opportunistic infections are associated with HIV-1?

A

Candida

25
Q

What protozoan opportunistic infections are associated with HIV-1?

A
  • Cryptococcus

- Pneumocystis (?)

26
Q

Where do p24 antigen levels spike?

A

Around 5-6 weeks - then it decreases and builds back up over a series of years

27
Q

When does anti-p24 antibody show up?

A

After p24 antigen. It spikes around 12 weeks, remains level for 10-12 years and then decreases over years

28
Q

When does the anti-env antibody show up?

A

Around 5 years and it remains close to level for up to 15-16 years

29
Q

What is p24?

A

A capsid protein encoded by gag

30
Q

What is the general timeline of HIV?

A
  1. Primary infection
  2. Acute HIV syndrome, Wide dissemination of virus, Seeding of lymphoid organs - Weeks 1-9
  3. Clinical Latency Week 9 - 8 years
  4. Constitutional symptoms - 8 years
  5. Opportunistic diseases - 9-10 years
  6. Death if untreated - 11 years
31
Q

What does the CD4+ T lymphocyte count look like in HIV?

A

It’s high/normal upon infection and decreases until week 6 to around 500.
Then it increases a little until week 12.
Then it slowly decreases over time until there aren’t any left.

32
Q

What does HIV RNA copies per mL plasma look like in infection?

A

It spikes initially around week 6.
Then it decreases a lot until week 9.
It remains steady/at lower/mid level
Starts to increase/spike again at 9 years and beyond.

33
Q

What test do you use to diagnose HIV?

A

ELISA

34
Q

What test do you use to confirm HIV?

A

Western blot

35
Q

What do you use to monitor patients with HIV?

A
  • CD4+ T cell enumeration by flow cytometery

- Polymerase chain reaction: viral RNA or DNA

36
Q

What is the goal of therapy for patients with HIV?

A

To reduce the level of circulating virus

37
Q

Which of the antiretroviral drugs targets a host protein?

A

Maraviroc - it binds specifically and selectively to host CCR5!

38
Q

How do you treat an alcoholic with liver failure and HIV?

A

-Give drug without hepatic side effects like NNRTIs (Tenofovir, Etravirine, Efavirenz), Enfuvirtide, Raltegravir, Maraviroc

39
Q

What HIV drug is important to avoid for patients with reduced renal function?

A

Tenofovir - Nucleotide reverse transcriptase inhibitor (only one of its class!)

40
Q

What is the main MUST KNOW toxicity of NRTIs?

A

Mitochondrial toxicity!! (can lead to lactic acidosis with hepatic steatosis (fatty liver) - potentially fatal!)

41
Q

What other side effects should you know about NRTIs?

A

Mitochdonrial toxicity, lactic acidosis, block mito polymerase, hepatic steatosis (fatty liver), fat redistribution, hyperlipidemia

42
Q

What are the main additional side effects of Zidovudine (NRTI)?

A

Granulocytonemia, anemia (bad for patients with bone marrow problems)

43
Q

What are the main additional side effects of Abacavir (NRTI)?

A

Hypersensitivity, allergic reactions

44
Q

What are the main additional side effects of Tenofovir (NRTI)?

A

Kidney issues

45
Q

What are the main side effects of Non-NRTIs?

A

Rash and GI, Drug interactions (cytochrome)

46
Q

What are the main side effects of protease inhibitors?

A

Drug interactions, peripheral lipoatrophy and central fat accumulation (skinny arms and large gut)

47
Q

What is important to know about Efuvirtide?

A

Fusion inhibitor

-Given via injection

48
Q

What should you know about Integrase inhibitor side effects?

A

Drug interactions (big issue!)

49
Q

What is gag and what does it create?

A

It’s a caspid protein. It creates p24.

50
Q

What does PCR tell you?

A

If the gene is present that you’re looking for. Looking at proviral stage (stage incorporated into the DNA of patient)

  1. Strand separation (denaturation)
  2. Primer binding (annealing)
  3. New DNA synthesis (extension)
  4. Exponential amplification
51
Q

What does RT-PCR tell you?

A

Measuring viral genomic RNA (don’t need to lyse cells to do this) - just looking at how many viral particles are floating around in the blood - take someones blood, spin out cells, then use plasma

52
Q

What is Flow cytometry?

A

Collect blood from patient, spin it down, get cells, attach fluorophores to CD4 using antibodies, lysis step to lyse all the red blood cells, send through flow cytometry machine (send entire population of lymphocytes though the machine) - typically machine looks for CD3 (all T cells), CD4 and CD8

53
Q

What is an indirect ELISA?

A

Looking for antibody to the virus (less expensive test) - initial HIV screening test

54
Q

What is a Western Blot?

A

Confirmatory testing - looking for protein, washing patient’s blood over screen –> screening serum for antibodies to multiple antigens at the same time

55
Q

What is Tropism testing?

A

Luciferase will show positive test result.

IHO Week 6 (16 decks)

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