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About the Authors:
Yuanjie Liu
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Hui Nie
Affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America
ORCID http://orcid.org/0000-0001-8827-8872
Richeng Mao
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Bidisha Mitra
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Dawei Cai
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Ran Yan
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
Ju-Tao Guo
Affiliation: Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
Timothy M. Block
Affiliation: Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
Nadir Mechti
Affiliation: CNRS, UMR5235, DIMNP, University of Montpellier 2, Montpellier, France
Haitao Guo
* E-mail: [email protected]
Affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
ORCID http://orcid.org/0000-0002-7146-916XAbstract
Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon ([epsilon]) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20D94G was unable to promote HBV RNA decay. Interestingly, ISG20D94G retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-[epsilon] interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV [epsilon] directly in absence of any other cellular proteins, indicating a direct [epsilon] RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade [epsilon]. In addition, the lower...