HIV Flashcards

1
Q

What genus is HIV?

What family is HIV?

A

Lentivirus

Retroviridae

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2
Q

What are the 3 steps characteristic of a retrovirus?

A
  • RT of genome RNA
  • Transfer of proviral DNA to nucleus
  • Integration of provirus into host chromatin
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3
Q

What are the 9 genes of HIV?

A

gag, pol, env, vif, vpu, vpr, nef, rev, tat

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4
Q

What is the receptor for HIV?

A

CD4
CCR5
CXCR4
on T helper cells

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5
Q

What is the role of cyclophilin A?

A
  • enables HIV to reverse transcribe.
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6
Q

What are the 2 active sites on a RT enzyme?

A

RNase active site

Polymerase active site

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7
Q

What are the 3 steps of HIV virus integration?

A
  1. Processing
  2. Joining
  3. Repair
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8
Q

What is the function of the Tat gene?

A
  • essential for infection
  • transactivator of transcription
  • binds to TAR
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9
Q

How does Tat affec gene expression?

A

Translation - may increase translation of HIV mRNA
Transcription - increased rate of initiation
Increased efficiency of elongation so increased processitivity of RNA Pol II

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10
Q

What occurs in the presence of Tat?

A

RNA polymerase complex is converted into a fully processive mode.
High proportion of initiation events leads to full length transcription.

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11
Q

What occurs in the absence of Tat?

A

HIV LTR assembles a poorly processive RNA polymerase complex - once clear of the promoter it frequently drops off producing truncated RNA.

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12
Q

What is TAR?

Where is it found?

A

Tat response element

Found immmediately downstream of txn start site

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13
Q

Describe how TAR is linked to Tat.

A

Tat works via a heterologous RNA binding domain which won’t act unless TAR is present.

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14
Q

What is Rev?

A

regulator of virion protein expression. Also essential for HIV replication.

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15
Q

What happens in the absence of Rev?

A

cytoplasmic mRNA for Gag, Pol and Env are reduced.

mRNA for Tat, Nef are unaffected.

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16
Q

What type of effect does Rev have?

A

Post transcriptional effect.

17
Q

What sequences are necessary for Rev function?

A

Sequences mapped to the Env coding region.

18
Q

What is the RRE

A

Rev response element, RRE is necessary for Rev to activate mRNA accumulation of an intron containing construct.

19
Q

Describe the function of the RRE

A

confers Rev-dependent export on mRNAs that contain it and would otherwise be retained.

20
Q

How does the RRE work?

A

Binds Rev at a high-affinity site in the RRE and Rev then multmerises on the RNA.

21
Q

What is the Rev activation domain?

A

A nuclear export signal which binds the exporting Crm1 and exits dependent on RAN.

22
Q

How does Rev relate to splicing

A

Export competes with splicing but splicing inhibition isnt the mechanism of Rev action.

23
Q

Describe the time course of translation of HIV proteins.

A

Early proteins: Tat and Rev and Nef
Tat are rev are transported to the nucleus where they act.
Late proteins: Gag, Pol, Env, accessory proteins vif, vpu, vpr. The expression of these depends on Tat and Rev

24
Q

How is Pol HIV protein produced?

A

Ribosomal frameshifting

25
Q

How does frameshifting occur??

A

Stem loop structure forms in HIV RNA, causes ribosome to pause on a slipperry sequence
10% of the time, the ribosome slips back on nucleotide then continues to translate Gag-Pol fusion protein

26
Q

How is env protein produced?

A
  • from 4kb species.

- co translationally inserted into the ER membrane.

27
Q

Where does glycosylation of gp120 region occur?

A

In the ER

28
Q

Where is the site of HIV particle assembly?

A

Env clusters in regions of the membrane high in lipids - lipid rafts.

29
Q

What is the packaging signal

A

Psi,

30
Q

What 2 signals do HIV RNAs contain

A
  • Dimerisation signal

- Packaging signal

31
Q

How are Gag-RNA complexes transported to regions of the membrane containing Env proteins to form the immature virus particle?

A

Cellular proteins called ESCRT complexes

32
Q

At which stage does HIV become an infectious virion

A

After the structural rearrangement

33
Q

What is the role of Vif?

A

inhibits host cell APOBEC3G, an antiviral enzyme which causes hypermutation of the HIV genome.

34
Q

What is the role of Vpu?

A

inhibits host cell tetherin, a cell surface molecule preventing the release of viral particles

35
Q

What is the role of Nef?

A

causes the downregulation of MHC Class I and CD4 from the cell surface.