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md1 - intersystems > 2. HIV > Flashcards

2. HIV Flashcards

1
Q

What behavioral and social factors contribute to heterosexually transmitted HIV epidemic?

A
  • Little/no condom use
  • Multiple partners
  • Overlapping sexual partners
  • Large sexual networks
  • Age mixing; old men & young girls
  • Women dependent on marriage/prostitution
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2
Q

What biological factos contribute to heterosexually transmitted HIV epidemic?

A
  • High STD rates (especially HSV-2)
  • High viral loads
  • Low rate of male circumcision
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3
Q

What family does HIV belong to?

A

Retroviridae

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4
Q

What is the HIV genome ?

A

Diploid linear 9.2kb + sense ssRNA

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5
Q

Where is the virus assembled?

A

Cytoplasm - plasma membrane

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6
Q

What is the origin of HIV-1

A

Evolved from SIVcpz (chimpanzee)

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7
Q

What is the origin of HIV-2

A

SIVsmm

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8
Q

What are the env genes?

A
  1. SU-surface (gp120) = cell attachment

2. TM-transmembrane (gp41) = fusion domain

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9
Q

What are the gag genes?

A
  1. MA-Matrix (p17)
  2. CA-Capdis (p24)
  3. NC-Nucleocapsid (p7)
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10
Q

What are the pol genes?

A
  1. RT-Reverse transcriptase (p66/51)
  2. IN-Interase (p31)
  3. PR-Protease (p11)
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11
Q

What is the function of the gag gene?

A

Structural proteins of the capsid, matrix, core and nucleocapsid

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12
Q

What is the function of the pol gene?

A

Viral enzymes, expressed as Gag-Pol polyprotein before autoclavage

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13
Q

What is the function of the env gene?

A

Envelope glycoproteins expressed from a spliced mRNA

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14
Q

What is the life cycle of HIV?

A
  • Binding
  • Reverse transcription
  • Provirus integrate into DNA
  • Transcription of regulatory protein
  • Re-uptake of regulatory protein back into nucleus (Rev)
  • Full length progeny RNA
  • Genomic RNA
  • Budding
  • Maturation
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15
Q

Describe the entry process of HIV-1

A
  • Attachment through non-specific cell receptors (CLR/Mannose R on Astrocytes)
  • Structural changes in gp120 after binding to CD4
  • Exposure of gp41 and binding to CCR5, CXCR4 promotes fusion and peptide insertion
  • Strucutural rearrangement of gp41 trimers drivers membrane fusion
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16
Q

What ligand blocks CCR5 HIV?

A
  • RNTES

- MIP-1a/b

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17
Q

What ligand blocks CXCR5

A

SDF-1

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18
Q

What functional mutation protects against HIV-1 ?

A

CCR-5 delta32

19
Q

What functional mutation protects against HIV2?

A

SDF-1

20
Q

What is the tropsm of CCR5 and CXCR4?

A

M (Macrophage) and T (T-cell) Trophic respectively

21
Q

Which of the HIV types induce syncythium ?

A

CXCR4

22
Q

Which of the HIV types is morep athogenic?

A

CXCR4

23
Q

What is the pathogenesis of HIV from Mucosal exposure to spread infection?

A
  • Mucosal exposure to HIV1
  • Selective infection by R5 strain
  • HIB binds to dendritic cell by DC-SIGN
  • Transport of virus to regional lymph nodes
  • Spread of infection to activated CD4+ T cells
  • Entry of virus infected cells into bloodstream
  • Dissemination
24
Q

What is the process of reverse transcription?

A
  • Converts viral genomic RNA into proviral cDNA

- Adds a U3 to the 5’ LTR and a U5 in the 3’ LTR

25
Q

Where can the virus integrate its DNA?

A

Resting and terminally differentiated Cells

26
Q

What is the function of the 5’ LTR

A
  • It acts as HIV gene promoter
  • Increase expressed in response to Tat protein
  • Silences HIV expression soon after initial replication
  • Responds to cellular proteins during T-cell activation
27
Q

What molecules are important for T-Cell activation and how does it relate to HIV?

A

NFkB and NFAT are important molecules to T-Cell activation in performing immune function.

These signals also activate integrated HIV genome by acetylating histones to open up DNA.

28
Q

What is the TAR RNA element?

A

It is the binding site for Tat to activate production of transcripton?

29
Q

That is the RRA?

A

It is the Rev-responsive RNA element, regulator of structural gene expression

30
Q

What is the function of Rev?

A

It stabilize and transports unspliced and partially spliced RRE+ HIB RNA to the cytoplasm to help express structural proteins

This is the early expression (regulatory and accessory proteins)

31
Q

What i the accessory proteins for?

A

It is not important for replication but modulates pathogenesis of the virus

32
Q

What is the function of Tet

A

Increases HIV gene transcription

33
Q

What are some proteins involved in HIV pathogenesis (Accessory proteins)?

A

Vif, Vpr, Vpu and Nef

34
Q

What is the function of Vif?

A

Blocks APOBEC3G proteins which is a cell defence targeting single stranded cDNA to promote infectivity of cell free virus

35
Q

What is the function of vpr?

A

Nuclear import of cDNA, cell growth arrest and weak transcription transactivation

36
Q

what is the function of Vpu?

A
  • Regulator of particle release and Env processing
  • Degrades MHC-1 and CD4 (via proteosome and lysosomal degradation)
  • Antagonizes TETHERIN
37
Q

What is the function of Nef

A

Down-regulate cell MHC-1 and CD4

38
Q

What is the function of TRIM5a?

A

Destabilization of the viral capsid

39
Q

What is the function of APOBEC3G

A

Lethal hyper-mutations

40
Q

What is the function of tetherin

A

Inhibition of virus release

41
Q

How many % of our genome are of retroviral origin?

A

8%

42
Q

Where does HIV particle mature?

A

After budding, Protease activity of Gag-Pol precursor protein causes cleavage of the polyproteins into individual proteins

43
Q

Where are the main latent HIV reservoir located?

A

T central and Transitional memory T cells

md1 - intersystems (7 decks)

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