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    World AIDS Day: HIV research at the Institut Cochin

    The study of the pathogenesis of infections by Human Immunodeficiency Viruses (HIV) is a strong and historical common interest of the Institut Cochin 3I department.

     

    The World AIDS Day gives the opportunity to present here an overview of research conducted at the Institute on HIV.  The Institut Cochin studies the early and late stages of the replicative viral cycle, characterizes the immune responses, the defense mechanisms of infected cells (T and B lymphocytes, macrophages, dendritic cells, platelets) and the escape of the virus from these defenses. The understanding of the molecular mechanisms governing viral latency and cytokine responses following infection of primary cell populations are also studied.

     

    HIV-1 is mainly transmitted to mucous surfaces during sexual intercourse. The "Mucosal entry of HIV and mucosal immunity" team studies how HIV-1 enters the genital tract, it identifies the mucosal reservoirs of HIV-1 established at the onset of the disease and the mechanisms of HIV dissemination despite efficient antiviral therapy.  In parallel, the team describes the neutralizing functions but also those mobilizing the innate immune cells, of protective IgA mucous antibodies developed by individuals resistant to infection despite unprotected sexual intercourse.

     

    The “Host-Virus Interaction” team explores the interactions between HIV-1 and the host cell in order to better understand the molecular mechanisms responsible for the spread of the virus in the host. In particular, the team dissects the mechanisms that target the integration of the viral genome into the chromosomes of the infected cell as well as those that control its expression. The team studies how HIV-1 hijacks cell trafficking and degradation pathways to promote its dissemination and thwart the host cell's intrinsic antiviral defenses.

     

    The "Immune Cell Signaling and Retroviral Infection" team seeks to understand how HIV is able to divert T lymphocyte signaling pathways, in order to optimize its intercellular dissemination and its replication in its target cells.

     

     

    One obstacle to eradicating HIV is the persistence of the virus in host cells despite highly effective antiretroviral therapy. Thus, the “Retrovirus, Infection and Latency” team is studying how the virus expresses is expressed in these reservoir cells or remains silent. The team addresses these topics at both fundamental and clinical levels.

     

    The "Dendritic cells, B lymphocytes and cytokines in their environment during viral infections and cancer" team has characterized dendritic cells, monocytes and reservoirs of HIV-2 infection to elucidate what makes this virus less pathogenic than HIV -1 (Immunovir study of the ANRS-CO5 cohort). It is working on the presentation of antigens by dendritic cells and on the eradication of T and macrophage reservoirs.

     

     

    HIV-1 persists within macrophages in specific compartments, disrupting normal cell functions, including their phagocytic and activating properties. The “Biology of phagocytes, infection and immunity” team studies these disturbed functions and viral production in macrophages.

     

     

     

     

    Recent publications

    • Diallo MS, Samri A, Charpentier C, [….], Brun-Vézinet F, Autran B; ANRS CO5 IMMUNOVIR-2 and ANRS CO15 ALT Study Groups. A Comparison of Cell Activation, Exhaustion, and Expression of HIV Coreceptors and Restriction Factors in HIV-1- and HIV-2-Infected Nonprogressors. AIDS Res Hum Retroviruses. 2020, Nov 12. doi: 10.1089/AID.2020.0084.
    • Duchemin M, Tudor D, Cottignies-Calamarte A, Bomsel M.  Antibody-Dependent Cellular Phagocytosis of HIV-1-Infected Cells Is Efficiently Triggered by IgA Targeting HIV-1 Envelope Subunit gp41. Front Immunol. 2020, 11:1141. doi: 10.3389/fimmu.2020.01141
    • Real F, Capron C, Sennepin A, […], Cramer Bordé E, Bomsel M.  Platelets from HIV-infected individuals on antiretroviral drug therapy with poor CD4+ T cell recovery can harbor replication-competent HIV despite viral suppression. Sci Transl Med. 2020, 12(535):eaat6263. doi: 10.1126/scitranslmed.aat6263.
    • Nguyen Quang N, Goudey S, Ségéral E, […], Emiliani S, Gallois-Montbrun S.  Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection. Retrovirology. 2020, 17(1):25. doi: 10.1186/s12977-020-00533-1.
    • Lepont L, Leymarie O, Berlioz-Torrent C. [Cellular and viral determinants control HIV-1 virus-containing compartment expansion in infected macrophages]. Med Sci (Paris). 2020, 36(1):20-23. doi: 10.1051/medsci/2019255.
    • Iannetta M, Isnard S, Manuzak J, [….], Cheynier R, Hosmalin A, on behalf of the IMMUNOVIR-2 study group (ANRS CO5 HIV-2 cohort). Conventional dendritic cells and slan monocytes during HIV-2 infection. “The Role of Dendritic Cells and Monocytes in HIV Infection”, Murray SM,  Cameron P. eds, Front Immunol 2020, DOI: 10.3389/fimmu.2020.01658.
    • Smith N, Bekaddour N, Leboulanger N, Richard Y, Herbeuval JP.  Isolation of Tonsillar Mononuclear Cells to Study Ex Vivo Innate Immune Responses in a Human Mucosal Lymphoid Tissue. J Vis Exp. 2020, 14;(160). doi: 10.3791/60914.
    • Borhis G, Trovato M, Ibrahim HM, Isnard S, Le Grand R, Bosquet N, Richard Y.  Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection. Front Immunol. 2020, 28;11:252. doi: 10.3389/fimmu.2020.00252.
    • Lê-Bury G, Deschamps C, Kizilyaprak C, Blanchard W, Daraspe J, Dumas A, Gordon MA, Hinton JCD, Humbel BM, Niedergang F. Increased intracellular survival of Salmonella Typhimurium ST313 in HIV-1-infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment. Biol Cell. 2020, Jan 10. doi: 10.1111/boc.201900055
    • Ganor Y, Real F, Sennepin A, [….], Hosmalin A, Bomsel M.  HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat Microbiol. 2019, (4):633-644.⟨10.1038/s41564-018-0335-z⟩
    • Roux A, Leroy H, De Muylder B, [….], Bismuth G, Mangeney M.  FOXO1 transcription factor plays a key role in T cell-HIV-1 interaction. PLoS Pathogens 2019, 15:e1007669.
    • Samri S, Charpentier C, Diallo M, [….], Brun-Vézinet F, Autran B., and the ANRS CO5 IMMUNOVIR-2 study group. Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection. PloS Pathogens 2019, 15:e1007758. doi: 10.1371/journal.ppat.1007758. hal-02165899
    • Chougui G, Margottin-Goguet F. HUSH, a Link Between Intrinsic Immunity and HIV Latency. Front Microbiol. 2019 Feb 12;10:224. doi: 10.3389/fmicb.2019.00224. Review.
    • Avettand-Fenoel V, Bayan T, Gardiennet E, [….], Lambotte O, Rouzioux C, for the CODEX ANRS Cohort Study Group. Dynamics in HIV DNA levels over time in HIV Controllers.  Journal of International AIDS Society 2019, 22:e25221 
    • Tremeaux P, Lenfant T, Boufassa F, [….], Meyer L, Avettand-Fenoel V, for the ANRS-SEROCO and PRIMO cohorts. Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection. EBioMed 2019, 10.1016/j.ebiom.2019.02.016.
    • [Noise from Vpx: "HUSH"!].  Chougui G, Martin M, Matkovic R, Etienne L, Margottin-Goguet F. Med Sci (Paris). 2019, 35(1):9-12. doi: 10.1051/medsci/2018312
    • Lucar O, Sadjo Diallo M, Bayard C, Samri A, Tarantino N, Debré P, Thiébaut R, Brun-Vézinet F, Matheron S, Cheynier R, Vieillard V; ANRS CO5 IMMUNOVIR-2 Study group.  B7-H6-mediated downregulation of NKp30 in natural killer cells contributes to HIV-2 immune escape. AIDS. 2019, 27;33(1):23-32. doi: 10.1097/QAD.0000000000002061.
    • Boncompain G, Herit F, Tessier S, […], Brelot A, Niedergang F, Perez F. Differential screening identifies molecules specifically inhibiting CCR5 transport to the cell surface and HIV infection. bioRxiv.Doi.org/10.101364927. Science Advances (2019); 5: eaax0821. doi: 10.1126/sciadv.aax0821
    • Roux A, Bracq  L, De Muylder B, […], Bismuth G, Mangeney M. FOXO1 transcription factor plays a key role in T cell – HIV-1 interaction. PLoS Pathog. 2019, 15(5):e1007669. doi: 10.1371/journal.ppat.1007669
    • Real F, Bomsel M. [HIV infection of the genital mucosa in real time]. Med Sci (Paris). 2019, 35(3):209-212. doi: 10.1051/medsci/2019044.
    • Prevedel L, Ruel N, Castellano P, Smith C, Malik S, Villeux C, Bomsel M, Morgello S, Eugenin EA.  Identification, Localization, and Quantification of HIV Reservoirs Using Microscopy. Curr Protoc Cell Biol. 2019, 82(1):e64. doi: 10.1002/cpcb.64.
    • Bomsel M, Lopalco L, Uberti-Foppa C, Siracusano G, Ganor Y.  Decreased Plasma Calcitonin Gene-Related Peptide as a Novel Biomarker for HIV-1 Disease Progression. AIDS Res Hum Retroviruses. 2019, 35(1):52-55. doi: 10.1089/AID.2018.0210
    • Leymarie O, Lepont L, Versapuech M, Judith D, Abelanet S, Janvier K, 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, 93(11):e00020-19. doi: 10.1128/JVI.00020-19.