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    Team: Host-virus interactions

     

    Team leaders

     

     

    THE TEAM IN BRIEF... Human Immunodeficiency Virus (HIV) infection is a dynamic process involving numerous rounds of infection, replication and cell death. HIV requires multiple interactions with cellular proteins and other cellular components to complete its viral replication cycle while at the same time escaping intracellular antiviral innate restriction mechanisms. Our team focuses on understanding the interplay between HIV and host cellular pathways. Our current research projects focus on two key steps of HIV life cycle: (1) HIV gene expression and (2) viral assembly, budding and release. Our team has a strong expertise in the identification of cellular cofactors of HIV proteins and the characterization of their mechanisms of action. Our work aims at understanding fundamental aspects governing HIV pathogenesis as well as novel cell host functions.

     

    Main results and Objectives

    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 heavily relies on the host cellular machinery to replicate. 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. Over the past 5 years, we demonstrated that LEDGF/p75, a cellular chromatin-associated protein controlling HIV integration also regulates HIV transcription. We characterized the role of RISC (RNA-induced silencing complex) in controlling HIV expression. We established the first dynamic picture of the cascade of splicing events taking place at early time points of infection in primary CD4+ T cells. We elucidated the role of trafficking and degradative pathways during HIV release and in cellular restriction imposed to HIV infection . We revealed new role of autophagic proteins in HIV countermeasure against viral restriction. We analyzed the interplay between the restriction factor BST2 and the viral protein Vpu during HIV production and the sequestration of HIV in macrophages.

     

    The Team

    The team “Host-virus Interactions” is co-headed by Clarisse Berlioz-Torrent and Stéphane Emiliani. The team was created by INSERM/CNRS/University of Paris in 2010 and renewed in 2014 and 2019. The team “Host-virus Interactions” is composed of 16 members, including 6 permanent members (4 researchers and 2 engineer), 3 Post docs, 4 PhD students, 1 engineer and 2 master students. 

    Two post-doctoral positions are currently open in the lab (update January 2021).

     

    December 2020

     

    News

     In progress

     

    Publications and patents

    Nguyen Quang N, Goudey S, Ségéral E, Mohammad A, Lemoine S, Blugeon C, Versapuech M, Paillart JC, Berlioz-Torrent C, Emiliani S, Gallois-Montbrun S. Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection. Retrovirology. 2020 Aug 17;17(1):25.

    Leymarie O, Lepont L, Versapuech M,  Abelanet S, Judith D, Janvier K and Berlioz-Torrent C. Contribution of the cytoplasmic determinants of Vpu to the expansion of virus containing compartments in HIV-1 infected macrophages. J Virol. 2019 May 15;93(11).

    Bonnard D, Le Rouzic E, Eiler S, Amadori C, Orlov I, Bruneau JM, Brias J, Barbion J, Chevreuil F, Spehner D, Chasset S, Ledoussal B, Moreau F, Saïb A, Klaholz BP, Emiliani S, Ruff M, Zamborlini A, Benarous R. Structure-function analyses unravel distinct effects of allosteric inhibitors of HIV-1 integrase on viral maturation and integration. J Biol Chem. 2018 Apr 20;293(16):6172-6186.

    Dejarnac O, Hafirassou ML, Chazal M, Versapuech M, Gaillard J, Perera-Lecoin M, Umana-Diaz C, Bonnet-Madin L, Carnec X, Tinevez JY, Delaugerre C, Schwartz O, Roingeard P, Jouvenet N, Berlioz-Torrent C, Meertens L, Amara A. TIM-1 Ubiquitination Mediates Dengue Virus Entry. Cell Rep. 2018 May 8;23(6):1779-1793.

    Amadori C, van der Velden YU, Bonnard D, Orlov I, van Bel N, Le Rouzic E, Miralles L, Brias J, Chevreuil F, Spehner D, Chasset S, Ledoussal B, Mayr L, Moreau F, García F, Gatell J, Zamborlini A, Emiliani S, Ruff M, Klaholz BP, Moog C, Berkhout B, Plana M, Benarous R. The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity. Retrovirology. 2017 Nov 9;14(1):50.

    Leymarie O, Lepont L, Berlioz-Torrent C. Canonical and Non-Canonical Autophagy in HIV-1 Replication Cycle. Viruses. 2017 Sep 23;9(10). pii: E270

    RoyN., PaciniG., Berlioz-Torrent C., and Janvier K. Characterization of E3 ligases involved in lysosomal sorting of the HIV-1 restriction factor BST2. J Cell Sci. 2017 May 1; 130(9): 1596-1611

    Eckenfelder,A., Ségéral, E., Pinzón, N.,  Ulveling, D., Amadori, C., Charpentier, M., Nidelet, S., Concordet, J-P., Zagury, J.-F. Paillart, J.-C., Berlioz-Torrent, C., Seitz, H., Emiliani S* and Gallois-Montbrun S*. Argonaute proteins regulate HIV-1 splicing in a Dicer independent manner. Nucleic Acid Res 2017 45 (7): 4158-4173. *corresponding author

    Madjo U.*, Leymarie, O.*, Fremont, F., Kuster, A., Gourhand, V., Gallois-Montbrun, S., Janvier, K. and C. Berlioz-Torrent. LC3C contributes to Vpu-mediated antagonism of BST2/Tetherin restriction on HIV-1 release through a non-canonical autophagy pathway. Cell Rep. 2016 Nov 22;17(9):2221-2233. *Co-first authors.

    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.

    Fremont, S., Gérard, A., Galloux, M., Janvier, K., Karess, R. E., Berlioz-Torrent, C. Beclin-1 is required for chromosome congression and proper outer kinetochore assembly EMBO Rep 2013 14(4):364-72

     

    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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