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    Equipe : Interactions hôte-virus

    Responsables

     

    L’EQUIPE EN BREF… 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.

     

     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.

    The lab studies the mechanisms of HIV latency leading to the persistence of cells harboring replication competent viruses that are transcriptionally silent. These reservoirs are established early during the course of infection and can survive for an extended period of time. If treatment is interrupted, viral rebound occurs rapidly. We are exploring the molecular basis of HIV expression both at the transcriptional and post-transcriptional levels.

    The lab also studies how HIV counteracts antiviral innate restriction during viral assembly and release. Host restriction factors, a set of proteins with direct antiviral activity, are an important facet of the innate immune response controlling infection in a cell-intrinsic manner. HIV has evolved countermeasures to escape these intrinsic antiviral innate restriction mechanisms. We are exploring how the interplay between cellular and viral factors controls HIV release and infectivity.

     

    Research impact

    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

    Breaking news – Nam Nguyen Quang, post-doc in the lab, published an article in Retrovirology presenting for the first time a wide landscape of the HIV-1 transcriptome in infected T cells thanks to the use of nanopore sequencing: https://retrovirology.biomedcentral.com/articles/10.1186/s12977-020-00533-1 Congratulations!

     

    Job opportunities – Two open post-doc positions in our lab for motivated postdocs to study HIV transcriptome and the role of autophagy machinery in HIV replication cycle. https://institutcochin.fr/la-recherche/3i/equipe-berlioz_torrent-emiliani/offres-demploi

     

    Oral communications

    - September 2020 – Sarah N’Da Konan, PhD student, presented her work on HIV-1 expression at the Sidaction Young Researchers Day.

    - October 2020 – Delphine Judith and Sarah Gallois-Montbrun have been selected to present their work at the ANRS AC41 International Symposium.

     

    Grants

    October 2020 – Sarah N’Da Konan has obtained a funding from La Fondation pour la Recherche Médicale (FRM) to pursue the fourth year of her PhD, in order to finalize her research project on the study of Epitranscriptomic regulation of HIV-1 expression. Thanks to La FRM for their support!

     

    Graduations

    - September 2020 – After four years in the Institut, Leslie Lepont has brilliantly defended her PhD on September 30th. She obtained the higher distinction and the Jury’s congratulations for her work on HIV-1 sequestration in macrophages.

    - October 2020 – Marjory Palaric obtained her Master diploma with honors and successfully obtained a scholarship from the prestigious "BioSPC" doctoral school to pursue her work on HIV-1 and autophagy.

    - December 2020 – Sophie Goudey has defended her PhD on the nuclear roles of Argonaute proteins in the regulation of HIV-1 expression on Dec 11th and received the Jury’s congratulations.

     

    New lab members

    Since last spring, we welcomed a new Post-Doc, 2 PhD candidates, a research engineer and a Master 2 student:

    - March 2020 – Fabienne Bejjani has joined the lab as a post-doctoral researcher 

    - October 2020 – Marjory Palaric and Corentin Aubé started their PhD with a scholarship from the "BioSPC" doctoral school: congrats and welcome!

    - January 2021 – Emilie Murigneux joined Sarah Gallois-Montbrun’s group as a research engineer to work on SARS-Cov2 interactome. The research project is funded by the ANR.

    - January 2021 – Louis Bergantz, student at ENS Paris-Saclay and Master 2 fellow in Genetics started his internship under the supervision of Sarah Gallois-Montbrun on HIV-1 splicing regulators.

     

    Scientific mediation

    - October 2020 – #FDS2021 Despite the actual Covid19 outbreak, our lab deployed all necessary efforts to welcome visitors in the strict respects of sanitary rules. Science enthusiasts had the opportunity to visit our lab, meet young researchers and learn how to track viral proteins by Western Blot. #FDS2021 was a great opportunity for the public to meet passionate scientists.  https://www.institutcochin.fr/animation/fete-de-la-science

    - November 2020 – #AC2021 Margaux, Melissa, Corentin and Angélique (from Florence Margottin and Claudine Pique’s lab) are overjoyed to supervise young pupils enrolled in the “Apprentis-chercheurs” program, directed by the association “L’arbre des connaissances”. This is a great opportunity for young students to discover the world of science that hopefully will fuel new ambitions! https://www.institutcochin.fr/animation/apprentis-chercheurs

    - April 2021 – Nam Nguyen Quang and Melissa Ait Said are part of the organizing committee of the 13th Symposium of JeCCo (Jeunes Chercheurs de l'institut Cochin) on "Sex in Science : a side effect?" to be held in Paris on April 6, 2021 https://jeccoteam.wixsite.com/jecco/intervenants

     

    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

    Methods and means for producing and isolating HIV latently infected cells. Inventors Stéphane Emiliani and Emmanuel Ségéral. N° EP14305885.7 deposited 05.08.14.

     

    Financial supports

    Equipes du département