Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins

Huizi Li; Wenhui Fan; Jie Min; Xiaoyuan Bai; Wenxian Yang; Heqiao Li; Yuna Zhao; Runshan Lin; Xiaojuan Jia; Wenjun Liu; Lei Sun

iScience (Dec 2023)

Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins

Huizi Li,
Wenhui Fan,
Jie Min,
Xiaoyuan Bai,
Wenxian Yang,
Heqiao Li,
Yuna Zhao,
Runshan Lin,
Xiaojuan Jia,
Wenjun Liu,
Lei Sun

Affiliations

Huizi Li: CAS 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
Wenhui Fan: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Corresponding author
Jie Min: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Xiaoyuan Bai: CAS 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, China
Wenxian Yang: CAS 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, China
Heqiao Li: CAS 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
Yuna Zhao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Runshan Lin: CAS 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
Xiaojuan Jia: CAS 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, China
Wenjun Liu: CAS 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 author
Lei Sun: CAS 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 author

Journal volume & issue: Vol. 26, no. 12
p. 108515

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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