Objective The efficient replication and spread of the Human Immunodeficiency Virus type 1 (HIV-1), the causative agent of the AIDS pandemic, requires that it parasitize an array of cellular proteins, many of which are unknown or uncharacterized, to facilitate its replication. In addition the virus must also defeat or subvert the human immune defences arrayed against it. Some of these immune defences, the innate retroviral restriction factors, have the capacity not only to directly interfere with the replication of the virus, but potentially to relay the information of its presence to activate a wider immune response – so called innate immune ‘sensing’. Molecular characterization of these processes for in vitro and in vivo replication of HIV-1 are essential for our understanding of the pathogenesis of HIV/AIDS. Additionally, it will provide strategies for the development of novel therapeutics for HIV treatment, and also potentially provide new paradigms that are applicable to other pathogenic mammalian viruses. To fill these gaps in our understanding this application seeks 5 years of ERC Starter Grant funding to explore two major research aims. Firstly we propose to characterize the interactions of retroviral restriction factors with the wider systemic immune response focusing on Tetherin/CD317/BST2 as a model system. In particular we will build on preliminary data suggesting that Tetherin can act as a general “pattern recognition molecule” for sensing assembling enveloped viruses by: A) transducing a proinflammatory signal and B) targeting nascent viral particles for antigen processing and presentation. Secondly we will apply novel genetic methods based on a haploid human cell line to identify, isolate and characterize human proteins that are required for early post-entry events in HIV replication or the function of the viral accessory protein Vpu. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencespublic healthepidemiologypandemicsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator KING'S COLLEGE LONDON Address Strand WC2R 2LS London United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Paul Labbett (Dr.) Principal investigator Stuart John Douglas Neil (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all KING'S COLLEGE LONDON United Kingdom EU contribution € 1 500 000,00 Address Strand WC2R 2LS London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Paul Labbett (Dr.) Principal investigator Stuart John Douglas Neil (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
