Identification of and molecular characterisation of a HIV restriction factor Lv2
Lead Research Organisation:
Queen Mary University of London
Department Name: UNLISTED
Abstract
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Technical Summary
The purpose of this Fellowship is to understand an anti-HIV activity Lv-2 in human cells. I propose an analysis of the cellular and molecular mechanisms underlying this restriction. That is we will
(1)Characterise how the viral genes, capsid (CA) and envelope (Env), avoid the factor. We have expertise on functional Env studies. For CA studies we will collaborate with Wes Sundquist an expert on viral CA. Also to develop techniques to analyse CA we will collaborate with Peter Stockley to make fluorescent aptamer probes to visualise CA microscopically.
(2) Identify the human gene that encodes this antiviral factor by screening logical candidate genes in collaboration with Prof Joe Sodroski who cloned TRIM5 (responsible for anti-viral factor Lv-1) and Dr Germana Meroni an expert on the TRIM family of proteins. Also we will search libraries of human genes.
(3) Investigate the pathways HIV takes to get from the plasma membrane to the nucleus. There are a number of routes by which viruses can traffic trough cells. Our data suggest that HIV can take at least two and that the potency of Lv-2 is dependent on the route taken. With Prof. Mark Marsh we will determine the restrictive and non-restrictive routes taken by HIV using dominate mutants and siRNA. Scientific and medical opportunities: The results will contribute to our understanding of HIV replication and pathogenesis, and to innate immunity to viral infection. They will also contribute to the understanding of trafficking of cell components and may suggest novel targets for the design and delivery of drugs to treat HIV.
(1)Characterise how the viral genes, capsid (CA) and envelope (Env), avoid the factor. We have expertise on functional Env studies. For CA studies we will collaborate with Wes Sundquist an expert on viral CA. Also to develop techniques to analyse CA we will collaborate with Peter Stockley to make fluorescent aptamer probes to visualise CA microscopically.
(2) Identify the human gene that encodes this antiviral factor by screening logical candidate genes in collaboration with Prof Joe Sodroski who cloned TRIM5 (responsible for anti-viral factor Lv-1) and Dr Germana Meroni an expert on the TRIM family of proteins. Also we will search libraries of human genes.
(3) Investigate the pathways HIV takes to get from the plasma membrane to the nucleus. There are a number of routes by which viruses can traffic trough cells. Our data suggest that HIV can take at least two and that the potency of Lv-2 is dependent on the route taken. With Prof. Mark Marsh we will determine the restrictive and non-restrictive routes taken by HIV using dominate mutants and siRNA. Scientific and medical opportunities: The results will contribute to our understanding of HIV replication and pathogenesis, and to innate immunity to viral infection. They will also contribute to the understanding of trafficking of cell components and may suggest novel targets for the design and delivery of drugs to treat HIV.