Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins
Summary: Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223025920 |
| _version_ | 1827582067533152256 |
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| author | Huizi Li Wenhui Fan Jie Min Xiaoyuan Bai Wenxian Yang Heqiao Li Yuna Zhao Runshan Lin Xiaojuan Jia Wenjun Liu Lei Sun |
| author_facet | Huizi Li Wenhui Fan Jie Min Xiaoyuan Bai Wenxian Yang Heqiao Li Yuna Zhao Runshan Lin Xiaojuan Jia Wenjun Liu Lei Sun |
| author_sort | Huizi Li |
| collection | DOAJ |
| description | Summary: Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1 (BNS1) and nucleoprotein (BNP). CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression. Meanwhile, CypA and the E3 ligase MIB1 competitively interact with BNP to inhibit its proteasomal degradation. Moreover, cyclosporine A treatment or CypA R55A mutation results in an impaired function of CypA in IBV replication. Notably, BNP hijacks CypA into the nucleus to enhance the activity of viral ribonucleoprotein complexes by enhancing the interaction between BNP and IBV polymerase basic protein 1. Taken together, this study unveils the critical role of CypA in facilitating IBV replication, suggesting that CypA is a promising target for anti-IBV drug. |
| first_indexed | 2024-03-08T22:45:12Z |
| format | Article |
| id | doaj.art-639de804e3114b26a90a1346a6922872 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:12Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-639de804e3114b26a90a1346a69228722023-12-17T06:41:03ZengElsevieriScience2589-00422023-12-012612108515Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteinsHuizi Li0Wenhui Fan1Jie Min2Xiaoyuan Bai3Wenxian Yang4Heqiao Li5Yuna Zhao6Runshan Lin7Xiaojuan Jia8Wenjun Liu9Lei Sun10CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Corresponding authorCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518107, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518107, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518107, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; The Biological Safety level-3 (BSL-3) Laboratory of Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518107, China; Corresponding authorCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorSummary: Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1 (BNS1) and nucleoprotein (BNP). CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression. Meanwhile, CypA and the E3 ligase MIB1 competitively interact with BNP to inhibit its proteasomal degradation. Moreover, cyclosporine A treatment or CypA R55A mutation results in an impaired function of CypA in IBV replication. Notably, BNP hijacks CypA into the nucleus to enhance the activity of viral ribonucleoprotein complexes by enhancing the interaction between BNP and IBV polymerase basic protein 1. Taken together, this study unveils the critical role of CypA in facilitating IBV replication, suggesting that CypA is a promising target for anti-IBV drug.http://www.sciencedirect.com/science/article/pii/S2589004223025920MedicineVirologyBiological sciences |
| spellingShingle | Huizi Li Wenhui Fan Jie Min Xiaoyuan Bai Wenxian Yang Heqiao Li Yuna Zhao Runshan Lin Xiaojuan Jia Wenjun Liu Lei Sun Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins iScience Medicine Virology Biological sciences |
| title | Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins |
| title_full | Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins |
| title_fullStr | Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins |
| title_full_unstemmed | Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins |
| title_short | Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins |
| title_sort | cyclophilin a facilitates influenza b virus replication by stabilizing viral proteins |
| topic | Medicine Virology Biological sciences |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223025920 |
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