Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β
| Autor: | Ainouze, Michelle, Rochefort, Pauline, Parroche, Peggy, Roblot, Guillaume, Tout, Issam, Briat, François, Zannetti, Claudia, Marotel, Marie, Goutagny, Nadege, Auron, Philip, Traverse-Glehen, Alexandra, Lunel-Potencier, Aude, Golfier, Francois, Masson, Murielle, Robitaille, Alexis, Tommasino, Massimo, Carreira, Christine, Walzer, Thierry, Henry, Thomas, Zanier, Katia, Trave, Gilles, Hasan, Uzma Ayesha |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Duquesne University [Pittsburgh], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Davoine, Laure-Hélène, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
Inflammasomes viruses [SDV]Life Sciences [q-bio] Interleukin-1beta Gene Expression Pathology and Laboratory Medicine Cervical Cancer Biochemistry Epithelium Animal Cells Medicine and Health Sciences Small interfering RNAs Biology (General) ComputingMilieux_MISCELLANEOUS [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology Human papillomavirus 16 Immune System Proteins Transcriptional Control Enzymes Nucleic acids Oncology Medical Microbiology Viral Pathogens Viruses Interferon Regulatory Factors [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology [SDV.IMM]Life Sciences [q-bio]/Immunology Cellular Types Anatomy Pathogens Oxidoreductases Luciferase Research Article Papillomaviruses [SDV.IMM] Life Sciences [q-bio]/Immunology QH301-705.5 Immunology Microbiology HPV-16 Extraction techniques Genetics Humans Gene Regulation Non-coding RNA Microbial Pathogens Immune Evasion Papillomavirus Infections Organisms Biology and Life Sciences Proteins Cancers and Neoplasms Epithelial Cells Cell Biology Oncogene Proteins Viral RC581-607 [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology RNA extraction Research and analysis methods Repressor Proteins Biological Tissue Gene Expression Regulation Enzymology RNA Immunologic diseases. Allergy [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology DNA viruses Gynecological Tumors |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2018, 14 (8), pp.e1007158. ⟨10.1371/journal.ppat.1007158⟩ PLoS Pathogens, 2018, 14 (8), pp.e1007158. ⟨10.1371/journal.ppat.1007158⟩ PLoS Pathogens, Vol 14, Iss 8, p e1007158 (2018) |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1007158⟩ |
| Popis: | Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses and to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a powerful cytokine produced when viral motifs are sensed by innate receptors that are members of the inflammasome family. Whether oncoviruses such as HPV16 can activate the inflammasome pathway remains unknown. Here, we show that infection of human keratinocytes with HPV16 induced the secretion of IL-1β. Yet, upon expression of the viral early genes, IL-1β transcription was blocked. We went on to show that expression of the viral oncoprotein E6 in human keratinocytes inhibited IRF6 transcription which we revealed regulated IL-1β promoter activity. Preventing E6 expression using siRNA, or using E6 mutants that prevented degradation of p53, showed that p53 regulated IRF6 transcription. HPV16 abrogation of p53 binding to the IRF6 promoter was shown by ChIP in tissues from patients with cervical cancer. Thus E6 inhibition of IRF6 is an escape strategy used by HPV16 to block the production IL-1β. Our findings reveal a struggle between oncoviral persistence and host immunity; which is centered on IL-1β regulation. Author summary Oncoviruses block innate immune responses to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a pro-inflammatory cytokine produced by the inflammasome pathway. Whether oncoviruses such as human papillomavirus (HPV) can activate the inflammasome remains to be explored. We demonstrated that keratinocytes, the host cell type for papillomaviruses, when infected with HPV16 induced IL-1β transcription and secretion. Yet, upon expression of the viral oncoprotein E6, IL-1β transcription was blocked. E6 expression inhibited IRF6 transcriptional regulation of the IL-1β promoter. Preventing E6 expression, or its ability to degrade p53, restored the ability of IRF6 to bind to the IL-1β promoter. HPV16 abrogation of p53, IRF6 and IL-1β expression was fully confirmed in cervical cancer cells and tissues from patients. These data highlight the equilibrium between the host innate immune rheostat and viral immune escape. |
| Databáze: | OpenAIRE |
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