TRAF3 Positively Regulates Host Innate Immune Resistance to Influenza A Virus Infection

Frontiers in Cellular and Infection Microbiology

Fangzhao Chen²  Jie Yang³  Yinyan Li³  Chunyu Zhang³  Liurong Chen³  Huiting Sang³  Shuofeng Yuan⁴ 

[1] Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China;Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, China;National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China;State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China;

关键词: TRAF3;    influenza A virus;    antiviral immunity;    type-I IFNs;    structural domain;   

DOI  :  10.3389/fcimb.2022.839625

来源: DOAJ

【 摘 要 】

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is one of the intracellular adaptor proteins for the innate immune response, which is involved in signaling regulation in various cellular processes, including the immune responses defending against invading pathogens. However, the defense mechanism of TRAF3 against influenza virus infection remains elusive. In this study, we found that TRAF3 could positively regulate innate antiviral response. Overexpression of TRAF3 significantly enhanced virus-induced IRF3 activation, IFN-β production, and antiviral response, while TRAF3 knockdown promoted influenza A virus replication. Moreover, we clarified that inhibiting ubiquitinated degradation of TRAF3 was associated with anti-influenza effect, thereby facilitating antiviral immunity upon influenza A virus infection. We further demonstrated the key domains of TRAF3 involved in anti-influenza effect. Taken together, these results suggested that TRAF3 performs a vital role in host defense against influenza A virus infection by the type-I IFN signaling pathway. Our findings provide insights into the development of drugs to prevent TRAF3 degradation, which could be a novel therapeutic approach for treatment of influenza A virus infection.

【 授权许可】

Unknown