Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response
| Autor: | Luis D. Giavedoni, Pierre Roques, Anne Sophie Liovat, Véronique Mayau, Beatrice Jacquelin, Michaela Müller-Trutwin, Cécile Butor, Brice Targat, Pierre Lebon, Arndt Benecke, Gaël Petitjean, Marie-Agnès Dillies, Désirée Kunkel, Guido Silvestri, Françoise Barré-Sinoussi |
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| Přispěvatelé: | Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Institut des Hautes Études Scientifiques (IHES), IHES, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unite de Recherches en Immunologie Humaine, Université de Montréal (UdeM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania, Southwest National Primate Research Center, Texas Biomedical Research Institute, Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint-Vincent de Paul, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), This study was supported by grants from Institut Pasteur (GPH no. 2) and ANRS (no. 03/172). Work in the Benecke group was funded by the 'Institut des Hautes Etudes Scientifiques,' the CNRS, the Genopole Evry, and the ANRS. Nonhuman cytokine detection was supported by NIH grant P51 RR013986. D. Kunkel and G. Petitjean received fellowships from ANRS and A-S. Liovat received a fellowship from the 'Ministère de l’Enseignement Supérieur et de la Recherche.', We are grateful to Roger Le Grand, Benoît Delache, Christophe Joubert, Xavier Montagutelli, Pascal Lavedan, and the staff of the CEA and Institut Pasteur animal facilities for excellent work in care of the animals used in this study. We thank Mickaël Ploquin and Bruno Vaslin for helpful discussions., Institut Pasteur [Paris], Institut des Hautes Etudes Scientifiques (IHES), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, Université de Montréal [Montréal]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Interferon Type I
animal diseases [SDV]Life Sciences [q-bio] MESH: Simian Immunodeficiency Virus Biology MESH: Virulence [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity MESH: Macaca mulatta MESH: HIV-1 03 medical and health sciences MESH: Gene Expression Profiling 0302 clinical medicine Immune system Downregulation and upregulation In vivo [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Gene expression MESH: Species Specificity MESH: Animals 030304 developmental biology 0303 health sciences MESH: Humans MESH: Virus Replication MESH: Host-Pathogen Interactions virus diseases MESH: CD4-Positive T-Lymphocytes General Medicine MESH: HIV Infections [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy Virology Phenotype MESH: Cercopithecus aethiops In vitro 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Immunology MESH: Oligonucleotide Array Sequence Analysis [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology [SDV.IMM]Life Sciences [q-bio]/Immunology Lymph MESH: Simian Acquired Immunodeficiency Syndrome MESH: Interferon-alpha Viral load 030215 immunology Research Article |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, 2009, 119 (12), pp.3544-55. ⟨10.1172/JCI40093⟩ Journal of Clinical Investigation, American Society for Clinical Investigation, 2009, 119 (12), pp.3544-55. ⟨10.1172/JCI40093⟩ |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/JCI40093⟩ |
| Popis: | African green monkeys (AGMs) infected with the AGM type of SIV (SIVagm) do not develop chronic immune activation and AIDS, despite viral loads similar to those detected in humans infected with HIV-1 and rhesus macaques (RMs) infected with the RM type of SIV (SIVmac). Because chronic immune activation drives progressive CD4+ T cell depletion and immune cell dysfunctions, factors that characterize disease progression, we sought to understand the molecular basis of this AGM phenotype. To this end, we longitudinally assessed the gene expression profiles of blood- and lymph node–derived CD4+ cells from AGMs and RMs in response to SIVagm and SIVmac infection, respectively, using a genomic microarray platform. The molecular signature of acute infection was characterized, in both species, by strong upregulation of type I IFN–stimulated genes (ISGs). ISG expression returned to basal levels after postinfection day 28 in AGMs but was sustained in RMs, especially in the lymph node–derived cells. We also found that SIVagm induced IFN-α production by AGM cells in vitro and that low IFN-α levels were sufficient to induce strong ISG responses. In conclusion, SIV infection triggered a rapid and strong IFN-α response in vivo in both AGMs and RMs, with this response being efficiently controlled only in AGMs, possibly as a result of active regulatory mechanisms. |
| Databáze: | OpenAIRE |
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