病毒学
癌症研究
细胞生物学
丙型肝炎病毒
内部收益率3
钻机-I
内部收益率1
泛素
受体
病毒复制
STAT1
泛素连接酶
作者
Mengying Xie,Yue Yin,Liqian Chen,Aiping Yin,Yan Liu,Yunzhi Liu,Lijun Dong,Qintao Lai,Jia Zhou,Liyun Zhang,Min Xu,Zhengliang Chen,Daming Zuo
出处
期刊:FEBS Journal
[Wiley]
日期:2020-01-01
卷期号:287 (2): 310-324
被引量:9
摘要
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 (TRAF3) and inhibit its K63-linked ubiquitination. Moreover, we provided evidence that SRA negatively regulates the stability of TRAF3 protein by promoting the recruitment of OTUB1 to TRAF3. Our findings indicate that SRA plays a crucial role in innate immune signaling by targeting TRAF3 for degradation and balancing the innate antiviral immunity.
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