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Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF 3 ubiquitination through recruiting OTUB 1
Author(s) -
Xie Mengying,
Yin Yue,
Chen Liqian,
Yin Aiping,
Liu Yan,
Liu Yunzhi,
Dong Lijun,
Lai Qintao,
Zhou Jia,
Zhang Liyun,
Xu Min,
Chen Zhengliang,
Zuo Daming
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15035
Subject(s) - innate immune system , biology , interferon , immune system , immunology , hepatitis b virus , virology , interferon type i , scavenger receptor , receptor , replicon , pattern recognition receptor , virus , plasmid , biochemistry , lipoprotein , dna , genetics , cholesterol
The battle between hepatitis B virus ( HBV ) infection and the host immune defense determines the outcome of the disease. Scavenger receptor A ( SRA ) is a phagocytic pattern recognition receptor involved in various cellular processes, including lipid metabolism, recognition, and clearance of pathogens or modified self‐molecules. Emerging evidence pointed out that SRA might act as an immunomodulator that contributes to innate immune defense against invading pathogens. Herein, we examined the role of SRA in the initiation of type I interferon ( IFN ) response to HBV infection and the virus clearance. Our results showed that SRA ‐deficient ( SRA −/− ) mice were resistant to HBV infection developed by hydrodynamic injection of HBV replicon plasmid. We found lower levels of HBV DNA and viral protein expression in SRA −/− mice, which was associated with enhanced type I IFN production, compared with wild‐type controls. Besides, we performed gain and loss of function experiments and determined that SRA inhibits innate antiviral immune responses to HBV . SRA could interact directly with tumor necrosis factor receptor‐associated factor 3 ( TRAF 3) and inhibit its K63‐linked ubiquitination. Moreover, we provided evidence that SRA negatively regulates the stability of TRAF 3 protein by promoting the recruitment of OTUB 1 to TRAF 3. Our findings indicate that SRA plays a crucial role in innate immune signaling by targeting TRAF 3 for degradation and balancing the innate antiviral immunity.