title: Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.
abstract: Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Abderaouf
authors.initials: A
authors.lastname: Damouche
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'anatomo-pathologie, Le Kremlin-Bicêtre, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lazure
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Laboratoire de Virologie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fènoël
authors.affiliation: Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Huot
authors.affiliation: INSERM, U1085-IRSET, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dejucq-Rainsford
authors.affiliation: INSERM, U1085-IRSET, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Satie
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Laboratoire de Virologie, Paris, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Laboratoire de Virologie, Paris, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: David
authors.affiliation: CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gommet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie clinique, Le Kremlin-Bicêtre, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noel
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Béclère, Service de Chirurgie Viscérale Minimale invasive, Clamart, France; INSERM U972, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pourcher
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Médecine Interne et Immunologie clinique, Clamart, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Martinez
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Chirurgie générale et digestive, Le Kremlin-Bicêtre, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Benoist
authors.affiliation: INSERM UMR S938, CDR Saint-Antoine; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Biochimie et Hormonologie; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Béréziat
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cosma
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Favier
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vaslin
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Laboratoire de Virologie, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: INSERM UMR S938, CDR Saint-Antoine; Sorbonne Universités, UPMC Univ Paris 6, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Biochimie et Hormonologie; ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.affiliation: Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Müller-Trutwin
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie clinique, Le Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bourgeois
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004197:Disease Reservoirs; D005260:Female; D006678:HIV / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008252:Macaca fascicularis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015434:Panniculitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology