Retroviruses and HIV Flashcards
PEP Regimen
Integrase Inhibitor + 2 NRTI’s given within 72 hours of infection
gp120
Surface envelope protein of HIV encoded on Env; Contains highly variable regions; Used for attachment
Technique to monitor HIV viral loads
RT-PCR
LTR
long term repeat; bind cellular and viral transcription factors (promoters and enhancers)
HIV Regulatory proteins
TAT, REV, and NEF
Mutation for HIV Resistance
CCR5 mutation; 10% of Caucasians are heterozygous, 1% are homozygous
Structural genes of HIV
Gag, Pol, and Env
Predictor of disease time course and progression to AIDS
viral load after acute infection
Nef
non-essential HIV protein that’s only required for disease progression; down-regulates CD4 and MHC Class I molecules
Defining feature of retroviruses
presence of Reverse Transcriptase
PrEP Regimen
Two NRTI’s taken daily
Properties of Oncoviruses
Can immortalize or transform cells because they contain growth-regulating oncogenes almost identical to genes involved in cellular growth
How is HTLV-1 transmitted
Sexually, through breastfeeding, and by IV drug use (US)
HIV Integrase Inhibitors
Inhibit HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
Drugs have “tegr” in middle
Raltegravir
Unique features of Reverse Transcriptase
Protein dimer that: 1) Can act as DNA Polymerase while using either RNA or DNA as template 2) Can remove RNA strand from RNA:DNA duplex
HIV protein that down-regulates CD4 and MHC Class I molecules
Nef
HIV Antibodies appear when?
3-8 weeks after infection
Preferred HIV co-receptor for sexual transmission
CCR5
Genes in genome of Retrovirus
Gag, Pol, Env, and LTR
Tax and HBZ
genes on HTLV-1 that promote viral gene expression and host cell cycle by binding to LTR or other cellular growth factors
HIV protein that stabilizes viral mRNA containing RRE by preventing splicing
Rev
Tat
HIV protein that acts as positive regulator of transcription by binding to region in LTR and recruiting RNA Polymerase II
Provirus
Virus that has integrated into genome
Treatment for HTLV-1
ATLL: anti-cancer therapy
TSP: antiretrovirals
gp40
transmembrane envelope protein of HIV encoded on Env
V3 Sequence
Can be used to predict whether HIV Strain will prefer CCR5 or CXCR4 as co-receptor
Diagnosis of HIV
4th Generation Diagnostic Test detects Antibodies to HIV-1 and HIV-2 as well as the p24 Antigen (which allows this test to work during window period). Confirmatory test needed to distinguish HIV-1 vs HIV-2. Previous tests performed immunoassays which only detected antibodies
Structure of Retroviruses
Enveloped, Icosahedral Viruses with two identical copies of Single Stranded Positive Sense RNA
gene that encodes reverse transcriptase, protease, and integrase
pol
gag
encodes the capsid and matrix proteins
Purpose of Combination Therapy
Virus is unlikely to mutate and develop resistance to three different mechanisms at once
HIV capsid protein and what gene it’s on
p24 Capsid encoded on Gag
HIV Protease Inhibitors
Competitive inhibitors of HIV protease that prevents cleavage of Gag and Pol precursor peptides thus preventing viral maturation to infectious form
Drugs have -navir suffix
Diseases caused by HTLV-1
- Adult T Cell Leukemia
- Tropical Spastic Paraparesis (myelopathy)
HIV-1 vs HIV-2
HIV-2 is less virulent and less common
When is LTR formed?
LTR’s are formed when a DNA copy is made from RNA by Reverse Transcriptase in order to allow integration into nucleus
Rev
HIV protein that stabilizes viral mRNA containing RRE by preventing splicing
env
gene that encodes surface and transmembrane proteins
Where is HTLV-1 prevalent
Japan and Carribean
Lentivirus family includes
HIV-1, HIV-2, and SIV
Diagnosis criteria for AIDS
1) CD4 T Cell Count < 200 per uL 2) certain opportunistic infections
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI’s)
Competitively inhibit nucleotide binding to reverse transcriptase and cause early termination; selectively inhibit HIV RT over host cell Polymerase.
Tenofovir is a nucleotide analog and does not require phosphorylation. Nucleoside analogs require phosphorylation before they are active
Receptors for HIV
CD4 with co-receptor CCR5 or CXCR4
Most important predictor of HIV disease stage
CD4 T Cell Count
pol
encodes reverse transcriptase, protease, and integrase
Important genes encoded on HTLV-1
tax and HBZ; HTLV-1 DOES NOT contain an oncogene.
These genes encourage expression of cellular growth factors and viral mRNA
HIV viral enzymes and what gene they’re on
Protease, Reverse Transcriptase, and Integrase on Pol; Reverse Transcriptase and Integrase are packaged within the viron
HIV Fusion Inhibitor (Enfuvirtide)
Blocks the fusion of gp41 on HIV envelope with host cell membrane
Gene that encodes the capsid
gag
Risk of HIV transmission from mother to fetus before ART vs after ART
30% vs < 2% ; women instructed not to breastfeed
Importance of Variable Regions
Allow Quasi Species of HIV to form within host which can allow the virus to evade immune detection or become better at binding CD4
HIV envelope proteins and what gene they’re on
gp120 and gp40 on Env
Multilobulated lymphocytes known as “Flower Cells” are seen in what disease?
Adult T Cell Leukemia caused by HTLV-1
bind cellular and viral transcription factors (promoters and enhancers)
LTR
HIV Entry Inhibitors (Maraviroc)
Block gp120 from binding to CCR5 (chemokine receptor antagonist); ineffective against HIV strains that bind CXCR4
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s)
Non-competitively bind to hydrophobic region of HIV Reverse Transcriptase Efavirenz, Nevirapine, Delavirdine
ARV regimen for HIV+ Patient
Two different NRTI’s + one of the following: 1) Integrase Inhibitor 2) NNRTI 3) Protease Inhibitor
Oncovirus Family includes what?
HTLV1
HIV Accessory Genes
Vif, Vpr, and Vpu; these genes are involved in manipulating the host cell and promoting its survival
gene that encodes surface and transmembrane proteins
env
HIV protein that acts as positive regulator of transcription by binding to region in LTR
Tat
