Intrahepatic homeobox protein MSX-1 is a novel host restriction factor of hepatitis B virus

Author:

Shen Zhongliang12ORCID,Zhang Shenyan1,Gao Zixiang2,Yu Xueping13,Wang Jinyu1,Pan Shaokun2,Kang Ning2,Liu Nannan2,Xu Huijun2,Liu Mu2,Yang Yang2,Deng Qiang2,Liu Jing24ORCID,Xie Youhua125ORCID,Zhang Jiming12

Affiliation:

1. Department of Infectious Diseases, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China

2. Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

3. Department of Infectious Diseases, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China

4. Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

5. Children’s Hospital, Fudan University, Shanghai, China

Abstract

Covalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo , and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.

Funder

MOST | National Natural Science Foundation of China

Shanghai Shen Kang Hospital Development Center

MOST | National Key Research and Development Program of China

Publisher

American Society for Microbiology

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