Viral Pathogenesis-HIV Flashcards
1
Q
Model of HIV
A
- diploid genome, occupies the core w/ other proteins and enzymes involved in rep
- HIV-1 (dominant, vpu is only in HIV1) and HIV-2
- small ORFs that give rise to accessory proteins
2
Q
HIV Virion Proteins (3)
A
- gag: group specific antigens (core proteins p24, p17, p9, p7)
- pol: polymerase (RT and integrase)
- env: envelope-gp160 cleaved to gp120 (receptor binding) and gp41 (fusion)
3
Q
Regulatory Auxiliary Proteins of HIV (2)
A
tat -transactivator of Tc -enhances Tc, binds TAR in LTR -decreases Tc of cell genes (eg. MHCII) rev -regulator of virion proteins -binds RRE (rev responsive element)-facilitates nuclear export of unspliced and partly spliced RNA
4
Q
Accessory Auxiliary Proteins of HIV (4)
A
- nef
- vif
- vpr
- vpu
5
Q
Accessory Auxiliary Proteins of HIV-nef
A
- negative reg. factor
- can increase or decrease virus infectivity
- downregs MHC-1, CD4, CD8
6
Q
Accessory Auxiliary Proteins of HIV-vif
A
- virion infectivity factor
- causes proteosomal degradation of cell APOBEC3G (cytidine deaminase which converts C to U and hyper mutates nascent minus strand reverse transcripts)
7
Q
Accessory Auxiliary Proteins of HIV-vpr
A
- viral protein R
- weak Tc activator
- causes G2 arrest (activates p21 cyclin-dependent kinase inhibitor)
- facilitates nuclear entry of preinteg complex
8
Q
Accessory Auxiliary Proteins of HIV-vpu
A
- viral protein U
- integral membrane glycoprotein mainly in ER/golgi
- disrupts env-CD4 complex-promotes CD4 degradation
- promotes budding, likely by removing CD4 trap in ER, allowing gp160 maturation
- antagonizes tetherin (binds newly produced viruses to cell to prevent spreading), allowing virus release from cell surface
9
Q
Consequences of HIV infection on host cell gene expression
A
- activation of cell Tc factors, gene expression
- integrated HIV DNA contains binding sites for cell Tc factors (eg. SPI, NF-kappaB, AP-1, NFAT-1)
- TAR element binds Tat
- NF-kappaB binding site: NK-kappaB stimulated by mitogens, cytokines
- upregulates Tc of all genes w/ NF-kappaB elements (IL-2, IL-2R, HIV)
10
Q
Progression to AIDs
A
- progressive course of declining immunity
- gradual decrease in CD4 pos. cells
- increased viral, bacterial and parasitic infection
- 1st symptoms are skin infections (bacterial, viral, fungal)
- later AIDs defining infections
11
Q
AIDs defining infections
A
- pneumonia (often parasitic)
- toxoplasmosis (parasitic infection of the brain)
- cryptosporidium (parasitic infection of intestinal tract)
- herpes virus infections (HSV, CMV)
12
Q
CD4 cell infection/depletion
A
- mucosal HIV infection results in drastic depletion of mucosal CD4 cells (effect on peripheral CD4 cells much less severe)
- CCR5+ memory T cells targeted for HIV infection and depletion
- CD4 cell depletion due to direct virus infection and virus induced Fas-mediated apoptosis
13
Q
Receptors for HIV
A
-CD4 present on CD4 T helper cells and macrophages
14
Q
Chemokine Receptor Usage-CCR5
A
- present on macs, Th cells, esp. memory T cells
- receptor for beta-chemokines (MIP-1alpha-CCL3, MIP-1beta-CCL4, RANTES-CCL5)
- used by M-tropic (R5) and T-tropic (X4) HIV
15
Q
Chemokine Receptor Usage-CXCR4
A
- fusin
- on macs, Th cells esp naive T cells
- receptor for stromal derived factor, SDF-1 (CXCL12)
- present on more cell types than CCR5
- used by T-tropic HIV (X4)
