Abstract
Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. During the HBV life cycle, HBV hijacks various host factors to assist viral replication. In this research, we find that the HBV regulatory protein X (HBx) can induce the upregulation of DExH-box RNA helicase 9 (DHX9) expression by repressing proteasome-dependent degradation mediated by MDM2. Furthermore, we demonstrate that DHX9 contributes to viral DNA replication in dependence on its helicase activity and nuclear localization. In addition, the promotion of viral DNA replication by DHX9 is dependent on its interaction with Nup98. Our findings reveal that HBx-mediated DHX9 upregulation is essential for HBV DNA replication.
Keywords:
DHX9; HBx protein; Nup98; hepatitis B Virus; ubiquitylation.
© 2019 John Wiley & Sons Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cell Nucleus / metabolism
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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DNA Replication
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DNA, Viral
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Gene Expression Regulation
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HEK293 Cells
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Hep G2 Cells
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Hepatitis B / genetics
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Hepatitis B / metabolism*
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Hepatitis B / virology
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Hepatitis B virus / physiology*
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Host Microbial Interactions
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Humans
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Mice
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Mice, Transgenic
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Pore Complex Proteins / metabolism*
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Trans-Activators / physiology*
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Up-Regulation
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Viral Regulatory and Accessory Proteins / physiology*
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Virus Replication
Substances
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DNA, Viral
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Neoplasm Proteins
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Nuclear Pore Complex Proteins
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Nup98 protein, human
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Trans-Activators
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Viral Regulatory and Accessory Proteins
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hepatitis B virus X protein
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DHX9 protein, human
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DEAD-box RNA Helicases