Section 3 slides, Part 2

Section 3 slides, Part 2 - 1 Early Transcription •...

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Unformatted text preview: 10/12/11 1 Early Transcription • Provirus DNA is transcribed making short mRNAs • Regulatory proteins transcribed • Translation of mRNAs into proteins – Use of host cell ribosomes • Early – Shorter mRNAs – First begins producing regulatory proteins (Tat, Nef and Rev) Translation • Later – Regulate shift from regulatory proteins to structural and enzymatic proteins. – Larger mRNAs synthesized (Tat) and exported out of nucleus (Rev) • ribosomes bind full-length RNA to make structural proteins (gag, pol and env). Role of Rev in HIV Lifecycle • Important for translation • Rev binds to the full-length HIV RNA • Aids in long RNAs to exit nucleus • Important for structural genes env , gag and pol Effects of Rev • Full-length genomic HIV RNA in cytoplasm à HIV genome • Large mRNAs translated into structural genes and enzymes « Capsid proteins, envelope proteins and viral enzymes would not be made « Virus would not be assembled • Other effects of Rev – Necessary for Tat expression – Acts like scorpion toxin on brain tissue 10/12/11 2 APOBEC3G • Immune cells (T cells, e.g.) synthesize the enzyme APOBEC3G • Has a powerful antiviral function • APOBEC3G degrades viral RNA, impairing the viruses infectivity • Induced mutations in viral genes make it impossible for new virions to be produced HIV Vif • APOBEC3G incorporated into forming virions • Vif localized to virion Regulatory protein - Vif • destroys APOBEC3G so that it can’t cause mutations in HIV genes in a newly infected cell • counteracts APOBEC3G protective effect • Both reduces the synthesis of and destroys existing APOBEC3G enzyme Processing of large proteins • Three large polyproteins : gag, pol and env – must be cleaved for functional virion • gag ⇒ matrix protein p17, capsid protein p24, and other smaller proteins • pol ⇒ the enzymes RT, IN and PR • env ⇒ the glycoproteins gp120 and gp41 Protease (PR) • PR is on pol • Autocleaves and released • Cleaves other polyproteins – Cytoplasm – Inside maturing virion – Essential for assembly and maturation of the virus • Reduced function PR makes non- infectious HIV virions Release of virus • Tetherin – cellular restriction factor • Vpu – counteracts tetherin 10/12/11 3 Other Negative Effects of HIV Components • Outlined in Reader Generally Mø = slow, low HIV production R5 viruses CD4+ T cells = rapid, high HIV production X4 viruses Linked to amount of CD4 expression Regulatory redux • RT copies viral RNA into DNA • vpr assists in carrying to nucleus • IN inserts viral DNA into chromosome to form provirus • LTR conversion to strong promoter – T cell activation – cytokines – nef, vpr enhances NF κ B • Enhanced RNApol activity – full length transcripts – tat • RNA transcripts transported to cytoplasm – rev • Translation of structural proteins/assembly of new virus – PR required, vpu utilized Treatment of HIV Disease • Antiviral agents that attack the virus...
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This note was uploaded on 12/06/2011 for the course BIOL 327 taught by Professor Peteringmire during the Fall '11 term at S.F. State.

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Section 3 slides, Part 2 - 1 Early Transcription •...

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