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    Team: Host-virus interactions

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    THE TEAM IN BRIEF... The Human Immunodeficiency Virus (HIV) infection is characterized by high levels of viral replication and spread even during the clinically latent stage of AIDS. Because of its limited coding capacity, HIV relies heavily on the host cellular machinery to replicate. Although several interactions between viral and cellular proteins have been described, identification of new host cofactors is crucial in order to understand the complex interplay between HIV and the host cell, as well as for the development of new anti-viral therapies targeting virus-host protein interactions. Our objective is to explore the relationship between HIV-1 and the host cell in order to gain insights into the molecular mechanisms underlying retroviral pathogenesis.

     

    Objectives

    Our projects focused on the characterization of these interactions during the different steps of HIV replication. We identified and functionally validated cellular cofactors controlling nuclear import and integration of the viral genome into the chromosome of the host cell. A second aspect of our studies concerned the late stages of viral replication, with a particular emphasis on trafficking of viral components to assembly sites, the budding and release of viral particles and their maturation. Once validated, these cellular cofactors potentially become new targets for the development of anti-viral therapies. The use of HAART (Highly Active Anti-Retroviral Therapies) for the treatment of HIV-infected patients has allowed considerable progress, both in terms of inhibition of the viral replication and also improvement of the clinical state of the patients. However, HAART do not eradicate HIV and cannot prevent the appearance of resistant viruses. A challenge in the development of future therapies will rely on the ability to inhibit key interactions between viral and cellular. Part of our effort consisted in the exploitation of our findings for the development of new antiviral molecules. The aims of our ongoing studies are:

    - Deciphering the dynamic interactions between HIV and host cell factors during early steps of replication, by focusing on the role of integrase partners involved in nuclear import and integration of the viral genome, and on the identification of cellular cofactor controlling HIV latency.

    - Characterizing the role of RISC (RNA-induced silencing complex) in controlling HIV expression

    - Understanding the mechanism of action of host factors involved in assembly, budding and release of viral particles, as well as Env incorporation within virions in infected T lymphocytes and primary macrophages.

    - Elucidating the role of trafficking and degradative pathways during HIV assembly and release, and in cellular restriction imposed to HIV infection.


    Main publications

    • Gérard A, Ségéral E, Naughtin M, Abdouni A, Charmeteau B, Cheynier R, Rain JC, Emiliani S. The integrase cofactor LEDGF/p75 associates with Iws1 and Spt6 for postintegration silencing of HIV-1 gene expression in latently infected cells. Cell Host Microbe. 2015 Jan 14;17(1):107-17.
    • Frémont S, Gérard A, Galloux M, Janvier, RE Karess, Berlioz-Torrent C. Beclin-1 is required for  chromosome congression and proper outer kinetochore assembly. EMBO reports 2013 14(4):364-72.
    • Gérard A, Soler N, Ségéral E, Belshan M, Emiliani S. Identification of low molecular weight nuclear complexes containing integrase during the early stages of HIV-1 infection. Retrovirology 2013 Feb 1;10:13.
    • Caillet M, Janvier K, Pelchen-Matthews A, Delcroix-Genête D, Camus G, Marsh M, Berlioz-Torrent C.Rab7A is required for efficient production of infectious HIV-1. PloS Pathog 2011, 7(11):e1002347.
    • Janvier K, Pelchen-Matthews A, Renaud JB, Caillet M, Marsh M, Berlioz-Torrent C. The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PloS Pathog 2011, 7(2):e1001265.

     

    Team’s news

    • Our lab is partner of the HIVinnov consortium (A collaborative European FP7 program).

    • Katy Janvier, Laureate of the  ANR Young investigator program 2013

    • Clarisse Berlioz-Torrent, Laureate of the prize FRM Line Renaud 2012

    • Team’s patents :

    International Patent WO 2008/08305909.7 - Novel substituted aryl derivatives, their process of preparation and their therapeutical uses. Inventors: R. Benarous, S. Berrut, J.M. Paris, S. Barbey, S. Emiliani, C. Berlioz-Torrent.

    International Patent WO2007/128806. Methods for in vitro screening of coumpounds inhibiting production of infectious HIV-1 and coumponds selected by said method.Inventors: C. Berlioz-Torrent, R. Benarous and S. Lopez-Vergès.          
    International Patent WO2003/046176: Protein-protein interactions in human immunodeficiency virus. Inventors: P. Legrain, J.C. Rain, R. Benarous, S. Emiliani, C. Berlioz-Torrent, G. Blot

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