Innate sensing of HIV-infected cells
| العنوان: | Innate sensing of HIV-infected cells |
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| المؤلفون: | Marion Sourisseau, Olivier Schwartz, Julien Pothlichet, Stephanie Louis, Mustapha Si-Tahar, Laurence Chaperot, Richard E. Randall, Helen K. W. Law, Alice Lepelley, Matthew L. Albert, Clémentine Schilte, Fabrizio Mammano, Joel Plumas |
| المساهمون: | Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre d'immunologie humaine (CIH), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Défense innée et inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Immunobiologie des Cellules Dendritiques, Université Joseph Fourier - Grenoble 1 (UJF), University of St Andrews [Scotland], University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gau, Mireille |
| المصدر: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2011, 7 (2), pp.e1001284. ⟨10.1371/journal.ppat.1001284⟩ PLoS Pathogens, 2011, 7 (2), pp.e1001284. ⟨10.1371/journal.ppat.1001284⟩ PLoS Pathogens; Vol 7 PLoS Pathogens, Vol 7, Iss 2, p e1001284 (2011) |
| بيانات النشر: | HAL CCSD, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | HIV Infections, Virus Replication, RIG-I, 0302 clinical medicine, Interferon, HIV Seropositivity, Lymphocytes, lcsh:QH301-705.5, Cells, Cultured, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, I interferon-production, Antiviral responses, virus diseases, 3. Good health, Integrase, Human-immunodeficiency-virus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Plasmacytoid dendritic cells, Virology/Immunodeficiency Viruses, Viral-infection, QR355 Virology, medicine.drug, Research Article, lcsh:Immunologic diseases. Allergy, Immunology, Blotting, Western, Microbiology, Virus, 03 medical and health sciences, CD4(+) T-cells, SDG 3 - Good Health and Well-being, Virology, Genetics, medicine, Humans, RNA, Messenger, Adapter protein, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Glycoproteins, QR355, Virion, HIV, Interferon-alpha, TLR7, Dendritic Cells, Hematopoietic Stem Cells, Reverse transcriptase, lcsh:Biology (General), Viral replication, Toll-Like Receptor 7, biology.protein, Parasitology, Interferon Regulatory Factor-3, Virology/Host Antiviral Responses, IFN-alpha, lcsh:RC581-607, IRF3, Alpha-interferon, 030215 immunology |
| الوصف: | Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection. Author Summary AIDS is characterized by a hyperactivation of the immune system. Innate and inflammatory responses, associated with an exacerbated production of cytokines like type I interferons (IFN) and of chemokines, deregulate the normal functioning of T lymphocytes and other cells. The events that trigger this inappropriate activation remain poorly understood. Plasmacytoid dendritic cells (pDCs) normally produce IFN when they encounter viruses. Here we examined how HIV-infected cells are recognized by pDCs, as well as by other immune and non-immune cells. We show that viruses transmitted via cell-to-cell contacts are more potent inducers of IFN than cell-free viral particles. In pDCs, recognition occurs in large part through TLR7, a cellular receptor detecting viral genetic materials after capture in intracellular vesicles. Donor cells expressing replication-defective viruses are also able to trigger IFN production by target cells. We further show that in TLR7-negative, non-hematopoietic cells an additional cytoplasmic pathway allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs at different intracellular localizations, and does not require ongoing viral replication. Characterization of the mechanisms of innate HIV-1 recognition allows a better understanding of the pathology of HIV infection, and has consequences for the design of vaccine strategies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e36055b304b97d62912779941de656d1Test https://hal-pasteur.archives-ouvertes.fr/pasteur-00590930Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e36055b304b97d62912779941de656d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537366 15537374 |
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