أعرض في EDS

Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

التفاصيل البيبلوغرافية
العنوان: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication
المؤلفون: Nadja Karl, Hanspeter Stalder, Mihyun Hwang, Luisa Cervantes-Barragan, Yize Li, Volker Thiel, Sabrina Marti, Philip V'kovski, Julia Spanier, Christina Gaughan, Markus Keller, Susan R. Weiss, Cornelia C. Bergmann, Robert H. Silverman, Cristina Gil-Cruz, Jochen Wilhelm, Matthias Habjan, Ulrich Kalinke, Frank J. M. van Kuppeveld, Burkhard Ludewig, Roland Züst, Huib H. Rabouw, Eveline Kindler, Ruth Elliot, John Ziebuhr
المساهمون: TWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany., dI&I I&I-1, LS Virologie
المصدر: PLOS Pathogens
Kindler, Eveline Patricia; Gil-Cruz, Cristina; Spanier, Julia; Li, Yize; Wilhelm, Jochen; Rabouw, Huib H; Züst, Roland; Hwang, Mihyun; V'Kovski, Philip; Stalder, Hanspeter; Marti, Sabrina; Habjan, Matthias; Cervantes-Barragan, Luisa; Elliot, Ruth; Karl, Nadja; Gaughan, Christina; van Kuppeveld, Frank J M; Silverman, Robert H; Keller, Markus; Ludewig, Burkhard; ... (2017). Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication. PLoS pathogens, 13(2), e1006195. Public Library of Science 10.1371/journal.ppat.1006195 <http://dx.doi.org/10.1371/journal.ppat.1006195>
PLoS Pathogens, 13(2). Public Library of Science
PLoS Pathogens
PLoS Pathogens, Vol 13, Iss 2, p e1006195 (2017)
بيانات النشر: Public Library of Science (PLoS), 2017.
سنة النشر: 2017
مصطلحات موضوعية: RNA viruses, 0301 basic medicine, Hydrolases, Coronaviruses, Cell Lines, viruses, Pathology and Laboratory Medicine, medicine.disease_cause, Biochemistry, White Blood Cells, Mice, Animal Cells, Medicine and Health Sciences, Coronaviridae, lcsh:QH301-705.5, Coronavirus, 630 Agriculture, biology, MDA5, Flow Cytometry, Enzymes, 3. Good health, Nucleic acids, RNA silencing, Ribosomal RNA, Medical Microbiology, Viral Pathogens, Viruses, Host-Pathogen Interactions, Biological Cultures, Cellular Types, Pathogens, Coronavirus Infections, Research Article, lcsh:Immunologic diseases. Allergy, Cellular structures and organelles, Nucleases, RNase P, Immune Cells, Nucleic acid synthesis, Immunology, RNA-dependent RNA polymerase, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, Microbiology, Viral Proteins, 03 medical and health sciences, Ribonucleases, Virology, DNA-binding proteins, Genetics, medicine, Animals, Humans, Chemical synthesis, RNA synthesis, Non-coding RNA, Microbial Pathogens, Molecular Biology, Immune Evasion, Blood Cells, Macrophages, Host Cells, Organisms, Biology and Life Sciences, Proteins, RNA, Cell Biology, Endonucleases, biology.organism_classification, Viral Replication, Immunity, Innate, Research and analysis methods, L929 Cells, Mice, Inbred C57BL, Biosynthetic techniques, 030104 developmental biology, lcsh:Biology (General), Viral replication, Enzymology, 570 Life sciences, Parasitology, lcsh:RC581-607, Ribosomes, Viral Transmission and Infection
الوصف: Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.
Author summary Coronaviruses are long known to be particularly successful in evading host innate immune responses. This manifests in barely detectable interferon responses during the first hours of infection and greatly facilitates establishment of robust virus replication. This phenotype of early innate immune evasion is common to all coronaviruses and can have detrimental consequences particular for infections with highly pathogenic coronaviruses, such as SARS-CoV and MERS-CoV. We therefore hypothesized that there must be an evolutionary conserved viral function that has evolved to prevent sensing of coronavirus infection by infected host cells. Our study now describes this function, namely the highly conserved coronavirus endoribonuclease activity. We found that coronaviruses that lack this enzymatic activity are readily visible to infected host cells that can now mount a swift and potent host response restricting virus replication within hours. Our study provides a new paradigm of a first layer of RNA virus innate immune evasion during the early phase of infection, that takes place at the site of RNA synthesis, and is based on removal of dsRNA that would otherwise trigger the simultaneous activation of cytoplasmic host cell sensors.
وصف الملف: application/pdf; image/pdf
تدمد: 1553-7374
1553-7366
DOI: 10.1371/journal.ppat.1006195
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5362c6e7567d79f689524cac2db3bcc2
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5362c6e7567d79f689524cac2db3bcc2
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15537374
15537366
DOI:10.1371/journal.ppat.1006195