Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary Macrophages
| العنوان: | Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary Macrophages |
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| المؤلفون: | François-Xavier Gobert, Bruna Cunha de Alencar, Matteo Gentili, Santy Marques-Ladeira, Jérémie Decalf, Célia Chamontin, Marylène Mougel, Marion Desdouits, Philippe Benaroch, Vasco Rodrigues |
| المساهمون: | Glia-Glia and Glia-Neuron Interactions in Neurophysiopathology Group (FR 3636), Fédération de Recherche en Neurosciences (FR 3636), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute of Molecular Virology, Universitätsklinikum Ulm - University Hospital of Ulm, Mougel, Marylene, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Journal of Virology Journal of Virology, 2017, 91 (15), ⟨10.1128/JVI.00147-17⟩ Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Journal of Virology, American Society for Microbiology, 2017, 91 (15), ⟨10.1128/JVI.00147-17⟩ |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Time Factors, [SDV]Life Sciences [q-bio], Immunology, Cell, Biology, Protein Serine-Threonine Kinases, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Interferon, Viral entry, Virology, medicine, Humans, LINFÓCITOS T, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, Viral Reverse Transcription, Innate immune system, Macrophages, virus diseases, Virus Internalization, Reverse transcriptase, Immunity, Innate, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Insect Science, Interferon Type I, HIV-1, Pathogenesis and Immunity, Interferon type I, medicine.drug |
| الوصف: | Along with CD4 + T lymphocytes, macrophages are a major cellular source of HIV-1 replication and a potential viral reservoir. Following entry and reverse transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid limits its cytosolic detection, enabling efficient replication. However, whether incoming HIV-1 particles are sensed by macrophages prior to reverse transcription remains unclear. Here, we show that HIV-1 triggers a broad expression of interferon (IFN)-stimulated genes (ISG) in monocyte-derived macrophages within a few hours after infection. This response does not require viral reverse transcription or the presence of HIV-1 RNA within particles, but viral fusion is essential. This response is elicited by viruses carrying different envelope proteins and thus different receptors to proceed for viral entry. Expression of ISG in response to viral entry requires TBK1 activity and type I IFNs signaling. Remarkably, the ISG response is transient but affects subsequent viral spread. Together, our results shed light on an early step of HIV-1 sensing by macrophages at the level of entry, which confers an early protection through type I IFN signaling and has potential implications in controlling the infection. IMPORTANCE HIV infection is restricted to T lymphocytes and macrophages. HIV-1-infected macrophages are found in many tissues of infected patients, even under antiretroviral therapy, and are considered a viral reservoir. How HIV-1 is detected and what type of responses are elicited upon sensing remain in great part elusive. The kinetics and localization of the production of cytokines such as interferons in response to HIV is of critical importance to understanding how the infection and the immune response are established. Our study provides evidence that macrophages can detect HIV-1 as soon as it enters the cell. Interestingly, this sensing is independent of the presence of viral nucleic acids within the particles but requires their fusion with the macrophages. This triggers a low interferon response, which activates an antiviral program protecting cells against further viral challenge and thus potentially limiting the spread of the infection. |
| تدمد: | 1098-5514 0022-538X |
| DOI: | 10.1128/JVI.00147-17⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7ea0effc99a9ecb83e5ed8b91ebeb36 https://pubmed.ncbi.nlm.nih.gov/28490595 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c7ea0effc99a9ecb83e5ed8b91ebeb36 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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| DOI: | 10.1128/JVI.00147-17⟩ |