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MITA / STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication
Shuhui Liu,
Kaitao Zhao,
Xi Su,
Lu Lu,
He Zhao,
Xianwen Zhang,
Yun Wang,
Chunchen Wu,
Jizheng Chen,
Yuan Zhou,
Xue Hu,
Yanyi Wang,
Mengji Lu,
Xinwen Chen,
Rongjuan Pei
PLOS
Published: January 5, 2017
Http://dx.doi.org/10.1371/journal.pone.016970
About the Authors
Shuhui Liu
Affiliations State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, University of Chinese Academy of Sciences, Beijing, China
Kaitao Zhao
Affiliations State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, University of Chinese Academy of Sciences, Beijing, China
Xi Su
Affiliations State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, University of Chinese Academy of Sciences, Beijing, China
Lu Lu
Current address: Jiangdong Center for Disease Control and Prevention, Ningbo, China
Affiliation Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
He Zhao
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Xianwen Zhang
Affiliations State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, University of Chinese Academy of Sciences, Beijing, China
Yun Wang
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Chunchen Wu
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Jizheng Chen
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Yuan Zhou
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Xue Hu
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Yanyi Wang
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Mengji Lu
Affiliation Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Xinwen Chen
* E-mail: [email protected] (RP); [email protected] (XC)
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Rongjuan Pei
* E-mail: [email protected] (RP); [email protected] (XC)
Affiliation State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Abstract
An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.
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发表于 2017-1-21 15:42
