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Rémi Cheynier Victor Appay Anne Hosmalin Gianfranco Pancino Vincent Vieillard Brigitte Autran

HIV-2: ANRS Immuno-Virological Network. Françoise Brun- Vezinet Charlotte Charpentier Diane Descamps Florence Damond Sophie Matheron Antoine Benard Rodolphe Thiebaut Geneviève Chêne. Rémi Cheynier Victor Appay Anne Hosmalin Gianfranco Pancino Vincent Vieillard Brigitte Autran.

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Rémi Cheynier Victor Appay Anne Hosmalin Gianfranco Pancino Vincent Vieillard Brigitte Autran

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  1. HIV-2: ANRS Immuno-Virological Network Françoise Brun-Vezinet Charlotte Charpentier Diane Descamps Florence Damond Sophie Matheron Antoine Benard Rodolphe Thiebaut Geneviève Chêne Rémi Cheynier Victor Appay Anne Hosmalin Gianfranco Pancino Vincent Vieillard Brigitte Autran + F Simon, F Clavel & M Benkirane & S Benichou

  2. A model of attenuated HIV infection in humans • Hypothesis: • preservation of the host immune resources due to reduced viral replication and limited immune activation • enabling stable capacity to control the viral infection Initial viral spread Restriction factors <-> Vpx like SIV, nef? Molecular characteristics of HIV-2? Distribution of cellular reservoir? Controlled viral replication Low viral load Dendritic cells? Monocytes? Controlled viral replication Limited chronic immune activation HIV-2 Low Type I IFN and IRG signature like AGM? Other Inflammatory cytokines? Immune preservation Good immune control Good immune reconstitution NK cells CD4 and CD8 responses: like controllers? Renewal capacity Low senescence? Low viral replication Progressors among HIV-2 infected patients Virtuous circle

  3. A model of attenuated HIV infection in humans Restriction factors <-> Vpx like SIV, nef? Molecular characteristics? Initial viral spread Initial viral spread Cellular reservoir? Uncontrolled viral replication Controlled viral replication Dendritic cells? Monocytes? Low viral load High viral load Controlled viral replication Uncontrolled viral replication Limited chronic immune activation Chronic immune activation Low Type I IFN and IRG signature like AGM? Other Inflammatory cytokines? HIV-2 HIV-1 Immune preservation Immune exhaustion Good immune control Good immune reconstitution Poor immune control Poor immune reconstitution NK cells CD4 and CD8 responses: like controllers? Low viral replication Renewal capacity Low senescence? Viral replication Vicious circle Virtuous circle

  4. 20 progressors starting ART B, C events CD4<500cells/µl CD4>500/µl with loss of >50C/y Immunological study at baseline and 1 year Reservoir study at baseline Pilot therapeutic trial with RAL containing regimen 20 non progressors Immunological study Reservoir study Study Population: ANRS CO5 HIV-2 cohort • 10 relatives, HIV negative healthy volunteers • Immunological study

  5. Immune correlates of disease protection in HIV-2 infection?(AO ANRS 2-2010) Innate and adaptative immunity in the control of HIV-2 infection? • Renewal capacity in lymphoid compartments R Cheynier • Preservation of immune resources (e.g. lymphoid progenitors, RTEs, thymic function); Higher thymic function and lower CD4 loss? • Cytokine production (IFN-I, inflammatory cytokines, Th1…) • T-cell activation and differentiation -Immunological senescence V Appay • Innate immunity • Functional study of dendritic cells (cDC, pDC, BDCA3+) A Hosmalin • Phenotype and functions of NK cells V Vieillard, • Anti-viral activity in CD8 compartments G Pancino

  6. HIV-2 Reservoir? (AO ANRS 1-2011) • Question • Is there a particular distribution of the HIV-2 reservoir in the CD4 T cells with a protection of the TCM cells and a larger reservoir size in the TTM cells as observed in Elite Controllers HIV-1 infected patients? • Is the HIV-2 viral replication limited in all suceptible cells, with comparable amount of proviral DNA in TCM and TTM CD4? • linked to the molecular characteristics of the viral replication?

  7. HIV2 Reservoir □ Quantification of HIV-2 reservoir • Plasma HIV-2 RNA (detection threshold at ≈4c/ml) • Intracellular HIV-2 DNA (total, integrated, 2LTR) in different cell compartments: PBMC, macrophages, naïve, TCM, TTM et TEM • Detection of infectious virus by co-culture and quantification of HIV-2 RNA in culture supernatants □Phylogenetic characterization of viruses • In the different lymphocyte subsets • As compared to plasma virus and to virus detected in total PBMCs • Restriction factors - host and virus sequences (SAMHD1-Vpx) □ Phenotypic and genotypic analyses of nefgene S Benichou

  8. Association of sCD14 and Inflammatory Markers with HIV-2 Disease Progression, ANRS CO5 (ICAAC 2011) R. THIEBAUT, R. ANTOINE, C. CHARPENTIER, F. DAMOND, A. TAIEB, G. CHENE, G. COLLIN, S. MATHERON, D. DESCAMPS, F. BRUN-VÉZINET. INSERM U897, Université Segalen, ISPED, Bordeaux, France;Laboratoire de Virologie, APHP, Bichat-Cl Bernard, Université P7, Paris, France; Service de Maladies Infectieuses et Tropicales, APHP, Bichat-Cl Bernard, Paris, France.

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