33 BIO 326R HIV - BIO 326R HIV Retroviruses Enveloped...

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BIO 326R HIV
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Retroviruses Enveloped positive strand RNA viruses Diploid genome (i.e. two identical copies of an RNA strand) RNA dependent DNA polymerase – Reverse Transcriptase Viral Particles will contain Two copies of genome Genome is polyadenylated and capped Multiple copies of Reverse Transcriptase and Integrase enzymes Lifecycle includes integration into host genome May be permanent - Integration may be into germline cells and be inherited
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Genes LTR – Long Terminal Repeat found at each end of RNA Regulatory sequences (not protein encoding) Strong promoters/enhancers Gag “group specific antigens” Capsid and matrix Pol - RT Env – glycoproteins for envelope Int – integrase Pro – protease
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HIV lifecycle GP120 on viral envelope binds to CD4 and/or coreceptor CCR5 Will infect monocytes, macrophages, neuroglial cells and T cells (macrophages have CD4 but CD4 T cells are still main target) GP120 may drift over time course of infection and bind to other receptors GP41 causes envelope to fuse with host cell membrane, capsid enters cytoplasm, RNA and associated enzymes released May also enter through endocytosis/phagocytosis RT uses tRNA as primer and makes DNA copy of genome RT has a high error rate First product is single-stranded cDNA RT also has an RNAse H activity – it degrades RNA in RNA:DNA hybrids Also acts as DNA-Dependent DNA polymerase – second strand of DNA synthesized to make dsDNA ds cDNA enters nucleus Integrase inserts ds cDNA into genome Viral genome inserted into genome = provirus Host RNA polymerase (Pol II) transcribes viral genes Long Terminal Repeats – sequences found at each end of a retroviral genome. LTRs are usually very strong promoters, but will have tissue restriction and mRNA production will vary depending on growth or activation of the host cell mRNAs will be capped and polyadenylated just like host mRNAs env expressed to make GP160 polyprotein, gag , and gag-pol transcribed and translated pro (protease) will cleave gag-pol protein into capsid and RT No protease activity means no production of active RT GP 160 processed by a host protease into GP120 and GP41 Viral particles released from cell through budding
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Binding of GP120 to CD4 receptor Fusion with cell membrane promoted by GP 41 RNA genomes, integrase and RT in cytoplasm, integrase goes to nucleus Synthesis of 1 st strand cDNA RNA degradation, 2 nd strand synthesis dsDNA goes into nucleus Viral DNA integrated into genome (prophage) Txn of viral genes and whole genome by host RNA pol Translation Synthesis of new viral proteins Processing by protease Budding of new viral particles Assembly and packaging Integrase RT pro mRNA genome
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HIV history Sequencing data indicates virus originated in humans as early as 1931, probably from chimpanzee SIV Perhaps 3 different occasions Other origin theories
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This note was uploaded on 07/24/2009 for the course BIO 52035 taught by Professor Edsatterwhite during the Spring '08 term at University of Texas at Austin.

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33 BIO 326R HIV - BIO 326R HIV Retroviruses Enveloped...

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