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24 Cards in this Set
- Front
- Back
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What is the HIV genome
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positive sense RNA
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Give 4 reasons why HIV is difficult to study
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1. few animal models
2. Only grows in a few cell types 3. Hetergeneous in an infected induvidual 4. long period before fatal immunodeficiency |
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How many people has AIDS killed as of 2009
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35 million
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What are the HIV high risk groups
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unprotected heterosexual contacted, male homosexual contact, IV drug use, comercial sex workers
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What is significant about the trend of HIV infection in the US
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it is not decreasing despite advanced in prevention knowledge and Tx. It has leveled off and is staying that way
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What are the sxs of inital HIV infection
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fever, headahce, rash, sore throat, swollen lymph nodes, fatigue
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how long will progression to AIDS take for someone with a viral load of 30,000 copies/ml
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80% progress to AIDS in 10 years or less, viral load is predictice of progression time
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What defines AIDS from HIV
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when the CD4 T cell count falls below 200 cells/ul, normal is 1000
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How are HIV accessory and regulatory genes expressed?
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Alternative splicing. Early in infection tat, rev and nef transcripts are spliced multiple times, late in infection vif, vpr, vpu, and env are singly spliced
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What is the fuction of HIV Tat
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Tat is an RNA binding protein that binds to TAR. when Tat binds to TAR it stimulates transcription from the HIV LTR by increasing elogation efficiency. the net effect is to increase the proportion of full length genomic RNA that is transcribed
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What is the fxn of the HIV regulatory gene Rev
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Rev is a regulator of viral mRNA production; it binds to the RRE and facilitates nuclear export of unspliced or singly spliced RNAs
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what is the function of the HIV accessory gene nef
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multiple fxns, regulates virus replication, reduces expression of MHC proteins and the CD4 receptor, enhances virion infectivity
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What is the function of the HIV accessory protein Vif
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Vif increases virus infectivity, affects virion assembly and/or viral DNA synthesis
it also interferes with host ABOBEC which protects the provirus from degradation |
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what is the function of the HIV accessory protein Vpr
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Vpr causes cell cycle arrest and facilitates nuclear entry of pre-integration complex
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What is the function of the HIV accessory protein Vpu
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Vpu affects virus release, disrupts the env/CD4 complex
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In what cell population is HIV LTR directed transcription most abundant? Why?
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activated T cells, activated T cells have lots of NF-kb which is important for transcription of full length HIV RNA
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Describe the molecular mechanism by which Tat stimulates transcription of the HIV LTR
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Tat inteacts with TAR (a hairpin structure) located at the 5' end of the HIV RNA. Tat binding recruits TfIIb and other elements of teh Tat-asscoiated kinase. This complex phosphorylates RNA pol II whcih makes the polymerase more efficient at processing down the template to make full length genomic RNA
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How is the balance/ shift between HIV early and late splciing events regulated
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The balance between early splicing events which make Tat, Rev, and Nef and late events which make Vif, Vpr, Vpu, and Env is regulated by teh level of Rev. After Rev is produced, it binds to RRE and reduces early splicing events increasing late splicing and transport of genomic RNA to the cytoplasm
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What unique feature must Rev have in order to bind RRE?
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REV must have a nuclear localization signal. Rev transcprits are exported to the cyotplasm where translation occurs. The protein must move back into the nucleus so that it can bind RRE on new transcripts and escort them to the cytoplasm before they are spliced.
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Aprox. how many people live w/ HIV today
How many people die of HIV per year in the US |
33 million live today, 16,000 per year die in the US
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Describe the molecular role of the HIV accessory protein vif
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In uninfected cells the ABOBEC protein recognizes proviral DNA and tags it for degradation. In an HIV infected cell, vif destroys ABOBEC by tagging it for ubiquitination. This allows the provirus to integrate into the host cell without being degraded
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Describe the constitution of teh HV env protein
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two sections make up the precurser gp160- SU gp120 and tm gp 41. A clevage reaction separates the protein into the surface receptor binding gp120 and the transmembrane domain gp41
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describe how env proteins regulate HIV entry into the host cell
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gp120 binds the CD4 receptor on the host cell and the complex interacts with the appropriate co-receptor. The fusion peptide of gp41 the inserts into the cell's membrane and begins the process of fusion between cell and virus
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What are the two possible co-receptors for HIV and what cells express them
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CXCR4- T cell tropic
CCR5- macrophage tropic these are both chemokine receptors |
