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Avian Metapneumovirus Subgroup C Phosphoprotein Suppresses Type I Interferon Production by Blocking Interferon Regulatory Factor 3 Nuclear Translocation.

التفاصيل البيبلوغرافية
العنوان: Avian Metapneumovirus Subgroup C Phosphoprotein Suppresses Type I Interferon Production by Blocking Interferon Regulatory Factor 3 Nuclear Translocation.
المؤلفون: Hou L; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Shi Y; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Guo J; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Sun T; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Wang D; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Yang X; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Liu C; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Cui Y; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Zhu N; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Tong X; College of Animal Science and Technology, Anhui Agricultural University, Hefei, China., Pan Y; College of Animal Science and Technology, Anhui Agricultural University, Hefei, China., Feng X; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Zhou J; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China., Liu J; College of Veterinary Medicine, Yangzhou University, Yangzhou, China.; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
المصدر: Microbiology spectrum [Microbiol Spectr] 2023 Feb 14; Vol. 11 (1), pp. e0341322. Date of Electronic Publication: 2022 Dec 20.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : ASM Press, 2013-
مواضيع طبية MeSH: Interferon Regulatory Factor-3*/genetics , Interferon Type I*/metabolism , Metapneumovirus*/metabolism , Metapneumovirus*/pathogenicity , Phosphoproteins*/genetics , Phosphoproteins*/metabolism, Animals ; Chickens ; Host-Pathogen Interactions ; Interferon-beta ; Viral Proteins/metabolism
مستخلص: Avian metapneumovirus subgroup C (aMPV/C) is an important pathogen that causes upper respiratory symptoms and egg production decline in turkeys and chickens. aMPV/C infection leads to inhibition of the host antiviral immune response. However, our understanding of the molecular mechanisms underlying host immune response antagonized by aMPV/C infection is limited. In this study, we demonstrated that the aMPV/C phosphoprotein (P) inhibits the IFN antiviral signaling pathway triggered by melanoma differentiation gene 5 (MDA5) and reduces interferon β (IFN-β) production and IFN-stimulated genes (ISGs) by targeting IFN regulatory factor 7 (IRF7) but not nuclear factor κB (NF-κB) in DF-1 cells. Moreover, we found that aMPV/C P protein only blocks the nuclear translocation of IRF3 by interacting with IRF3 in HEK-293T cells, instead of affecting IRF3 phosphorylation and inducing IRF3 degradation, which suppresses IRF3 signaling activation and results in a decrease in IFN-β production. Collectively, these results reveal a novel mechanism by which aMPV/C infection disrupts IFN-β production in the host. IMPORTANCE The innate immune response is the first defense line of host cells and organisms against viral infections. When RNA viruses infect cells, viral RNA induces activation of retinoic acid-induced gene I and melanoma differentiation gene 5, which initiates downstream molecules and finally produces type I interferon (IFN-I) to regulate antiviral immune responses. The mechanism for avian metapneumovirus (aMPV) modulating IFN-I production to benefit its replication remains unknown. Here, we demonstrate that phosphoprotein of aMPV subgroup C (aMPV/C) selectively inhibits the nuclear translocation of interferon regulatory 3 (IRF3), instead of affecting the expression and phosphorylation of IRF3, which finally downregulates IFN-I production. This study showed a novel mechanism for aMPV/C infection antagonizing the host IFN response.
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فهرسة مساهمة: Keywords: IFN-β production; IRF3; avian metapneumovirus subgroup C; nuclear translocation; phosphoprotein
المشرفين على المادة: 0 (Interferon Regulatory Factor-3)
0 (Interferon Type I)
77238-31-4 (Interferon-beta)
0 (Phosphoproteins)
0 (Viral Proteins)
تواريخ الأحداث: Date Created: 20221220 Date Completed: 20230306 Latest Revision: 20230412
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9927154
DOI: 10.1128/spectrum.03413-22
PMID: 36537793
قاعدة البيانات: MEDLINE
الوصف
تدمد:2165-0497
DOI:10.1128/spectrum.03413-22