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Immunology / Micro > Retroviruses - HIV / AIDS > Flashcards

Retroviruses - HIV / AIDS Flashcards

1
Q

What is the definition of a retrovirus?

A

A virus which uses a reverse transcriptase to transcribe a ssRNA to a dsDNA

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2
Q

Why is HIV called a Lentivirus?

A

Lenti - means slow

It is a slowly progressing disease

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3
Q

What are the two types of HIV and which one is more virulent?

A

HIV-1 and HIV-2. HIV-2 is more like SIV, but HIV-1 is worldwide and highly virulent

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4
Q

What are the three tropisms of HIV? What is HAD?

A

M-tropic - Macrophages - binds CCR5 as coreceptor
T-tropic - CD4+ T cells - binds CXCR4 as coreceptor
Microglia - results in the neurologic disorders such as HIV-associated dementia (HAD)

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5
Q

What is the primary receptor of HIV for all the forms?

A

CD4 - the tropism only changes the co-receptor

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6
Q

What is the first stage of HIV infection called and how does this relate to infectiousness? How does this relate to antibodies and CD4 count?

A

Acute Retroviral Syndrome - within 1-3 months of HIV infection. Flu-like symptoms, with highest viral loads until the patient dies.

HIV loads will fall as anti-HIV antibodies develop. CD4 cells will also recover as this happens

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7
Q

What is the second stage of HIV and what is happening during this time?

A

The clinical latency stage, typically lasting 8-10 years

It is the asymptomatic stage where the CD4 cell temporarily rises, and then HIV copy number declines. There will be a slow trend of CD4 count downward during this stage.

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8
Q

What is the “viral set-point”?

A

The stabilized plasma concentration of virus after the peak of primary infection, it is the equilibrium met between cytotoxic T cell killing and viral replication in CD4 cells.

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9
Q

What is the cutpoint for development of AIDS? Lasts 2-3 years

A

CD4+ count is less than 200 cell / mL, making you very vulnerable to opportunistic infections.

Lasts 2-3 years typically

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10
Q

What are long-term non-progressors?

A

Minority of peak infected with HIV - low virus levels with elevated CD4+ count and no antiretroviral treatment

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11
Q

What are three ways to be a long-term non-progressor?

A
  1. Mutations in CCR5 - slows progression
  2. Higher levels of CCR5-binding ligands - compete with HIV
  3. APOBEC3 - high levels of proteins which counteract reverse transcriptase
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12
Q

What is the HIV virus structure?

A

Two identical + sense RNA strands, spherical capsid, enveloped retrovirus

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13
Q

How many genes are in the HIV genome and what classes are they?

A

9 genes:
3 structural
2 Regulatory
4 Accessory

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14
Q

What is the function of gp120?

A

Part of viral envelope, binds to CD4 and CCR5 or CXCR4

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15
Q

What does gp41 do with respect to gp120?

A

gp41 is another envelope protein, penetrates through cell membrane and facilitates fusion between virus and human cell

This fusion releases the capsid into the cytoplasm

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16
Q

What is the function of Pol? What proteins does it yield?

A

Cleavage of Pol precursor yields the Protease, Reverse Transcriptase, and Integrase enzymes

17
Q

What does HIV do once it’s capsid is in the cell?

A

Viral RNA is reverse transcribed by RT into dsDNA. Integrase enzyme gets it into the genome

18
Q

What proteins are responsible for transcription and export?

A

The two regulatory proteins: Tat and Rev

Tat = enhances RNA transcription (transcriptional activator)
Rev = prevents RNA splicing in the nucleus before export
19
Q

Where does HIV-1 virus assembly begin? What genes are first transcribed?

A

At the plasma membrane, Gag and Pol precursors are transcribed first

20
Q

When does release happen?

A

The three structural proteins Env, Gag, and Pol assemble with the viral RNA genome and acquire their envelop by passing out of the host membrane

21
Q

What happens in the maturation step?

A

Outside of the cell, with envelope acquired, the viral protease (made from Pol protein in the cell) cleaves precursor Gag and Pol proteins to make mature infectious virus particle

22
Q

What proteins are a part of Gag?

A

Matrix
Capsid
Nuclear Capsid

23
Q

What is Env protein before cleavage?

A

Env = gp160, cleaves into gp120 (surface) and gp41 (transmembrane)

24
Q

What is the definition of HIV accessory proteins?

A

They are non-essential. Virus can replicate in vitro without them, but they are needed for in vivo pathogenesis

25
Q

What are the four HIV accessory proteins?

A

Nef
Vif
Vpr
Vpu

26
Q

What is Nef?

A

Accessory protein for immune evasion by downregulating CD4 and MHC Class 1

e = evasion

27
Q

What is Vif?

A

Virion infectivity factor - counteracts host cytidine deaminases which degrades reverse transcribed viral DNA

28
Q

What is Vpr?

A

Viral protein R - infection of nondividing cells such as macrophages, induces a cell cycle arrest and apoptosis

R = arrrrrrrrrrrrrrrrrrrrrrrrest

29
Q

What is Vpu?

A

Viral Protein U - Promotes virus bUdding

30
Q

What are the cellular reservoirs of HIV?

A

Infected CD4+ cells, macrophages, and DCs

Even ASTROCYTES!

31
Q

What is it so difficult to fully eradicate HIV?

A

Anatomical reservoirs = sanctuaries. Such as the CNS, male genital tract, and lymphoid tissue. Antivirals cannot get to these sites and their are immuneprivileged. Cannot cross BBB

32
Q

How is HIV diagnosed?

A

ELISA or Western blot (for protein)

33
Q

What is HAART / its definition?

A 
Highly active anti-retroviral therapy
Combination of 3 or more drugs from at least 2 classes:
1. Nucleoside analogs RT inhibitors
2. Non-nucleoside analog RT inhibitors
3. Entry inhibitors
4. Protease inhibitors
5. Integrase inhibitors
34
Q

What is the first identified human onco-retrovirus? What family is it in?

A

Human T-cell Leukemia Virus (HTLV)

Belongs to Deltavirus genus

35
Q

What are the two main diseases caused by HTLV-1?

A

Adult T-cell Leukemia (ATL)

Tropical spastic paraparesis / HTLV-1 associated myelopathy (TSP/HAM)

36
Q

What is the transmission of HTLV-1?

A

Vertical, sexual, or blood / IVDU

37
Q

Where is HTLV-1 prevalent?

A

Australia, Caribbean, South America, Central + West Africa, South Japan

38
Q

What is the treatment for HTLV-1?

A

IFN-alpha and zidovudine

39
Q

What provides temporary relief from TSP?

A

Zidovudine, danazol (a steroid), and vitamin C

Immunology / Micro (56 decks)

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