Human immunodeficiency Virus

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HIV replication in a cell. A quick look into what we know

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Human immunodeficiency Virus:

Human immunodeficiency Virus -Varun C N

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Varun C N- HIV replication 2 Declaration All the materials that is shown in the slide has been taken from various sources (Which has been sited as appropriate) . The Non cited materials have been taken from public domains. None of them involves any of my work and hence I don’t claim any intellectual property rights over any of them. The material has been prepared only for educational purpose and I don’t take any personal responsibility for the matter produced. I have however taken maximum care to make data as reliable as possible Varun C N Feb 2012

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Gene Expansion Functions/ Proteins encoded gag Group-specific antigen Virus core proteins. Gives rise to MA (matrix), CA (capsid), NC (nucleocapsid), p6 pol Polyprotein PR (protease), RT (reverse transcriptase), IN (integrase) env Envelope Envelope glycoproteins tat Trans-activator of transcription Enhances viral replication and activates CD4 nef Negative regulatory factor Promotes CD4 activation, blocks cellular apoptosis, enhances infection rev Regulator of virion protein expression Regulates RNA nuclear export vpr Viral protein R Unique to HIV-1 Promotes cell cycle blocking vif Virion infectivity factor Stabilizes reverse transcriptase and overcomes the inhibition by the APOBEC3G. vpu Viral Protein U Promotes release of the virions from CD4 vpx Virion protein Found in HIV 2 Homolog of HIV-1 vpr 5 Varun C N- HIV replication

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Structure of core gp120 Peter D. Kwong etal; Structure of an HIVgp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature , Vol 393,18 june 1998 CD4–gp120 interactions: Ribbon diagram of gp120 (red) binding to CD4 (yellow). 7 Varun C N- HIV replication

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Binding of CD4 to gp120 causes expression of the V3 loop The V3 loop being flexible extends to target cell membrane. Loop acts a latch to the CCR5 or CXCR4 V3 interacts with both N terminus and 2 nd extracellular loop of CCR5 Cause release of gp41 gp41 inserts to the cell membrane gp41 rearranges and brings the HR1 and HR2 domains to form a 6- bundle shape. Pulls the virus and cell membrane further close and cause fusion 8 Varun C N- HIV replication

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Joseph P. McGowan, Published online at www.prn.org: The PRN Notebook ® Volume 15, January 2010 9 Varun C N- HIV replication

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The conformations of HIV-1 gp41 Michael B Zwick, Erica O Saphire & Dennis R Burton; gp41: HIV's shy protein. Nature Medicine  10, 133 - 134 (2004) 10 Varun C N- HIV replication

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Model of HIV coreceptor (CCR5 and CXCR4) utilization and inhibition of HIV entry by co receptor ligands. Entry of R5 (i.e., predominantly macrophage- tropic) strains of HIV is blocked by the CCR5 ligands MIP-1α, MIP-1β, and RANTES. Entry of X4 (i.e., predominantly T-cell–tropic) strains of HIV is blocked by the CXCR4 ligand SDF-1. 11 Varun C N- HIV replication

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Bettina Stolp and Oliver T. Fackler How HIV Takes Advantage of the Cytoskeleton in Entry and Replication. Viruses 2011, 3, 293-311. Open access 12 Varun C N- HIV replication

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Michael bukrinsky, A Hard Way to the Nucleus; Molecular Medicine, January – June 2004, Volume 10, Number 1 – 6. 13 Varun C N- HIV replication

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Giuseppe la Regina etal. Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors. Review. Antiviral chemistry and chemotherapy 2010;20:213-237 14 Varun C N- HIV replication

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Cui J, Tungaturthi PK, Ayyavoo V, Ghafouri M, Ariga H, Khalili K, Srinivasan A, Amini S, Sawaya BE. The role of Vpr in the regulation of HIV-1 gene expression. Cell Cycle. 2006 Nov; 5(22): 2626-38. 15 Varun C N- HIV replication

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Souad Naji etal. Host cell interactome of HIV-1 Rev includes RNA helicases involved in multiple facets of virus production. Published on December 15, 2011. Copyright 2011 by The American Society for Biochemistry and Molecular Biology, Inc 28 Varun C N- HIV replication

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Giuseppe la Regina etal. Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors. Review. Antiviral chemistry and chemotherapy 2010;20:213-237 35 Varun C N- HIV replication

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Varun C N- HIV replication 37 Thank you for your kind attention You can also follow me at my blog. www.microboids.net