Abstract
Human hepatitis B virus (HBV) infection remains a serious health problem worldwide. However, the mechanism for the maintenance of HBV in a latent state within host cells remains unclear. Here, using single-cell RNA sequencing analysis, we identified four genes linked to the maintenance of HBV in a liver cell line expressing HBV RNA at a low frequency. These genes included DOCK11 and DENND2A, which encode small GTPase regulators. In primary human hepatocytes infected with HBV, knockdown of these two genes decreased the amount of both HBV DNA and covalently closed circular DNA to below the limit of detection. Our findings reveal a role for DOCK11 and DENND2A in the maintenance of HBV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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DNA, Viral / genetics
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Guanine Nucleotide Exchange Factors / metabolism
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Hep G2 Cells
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Hepatitis B / metabolism*
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Hepatitis B / physiopathology
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Hepatitis B virus / pathogenicity
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Hepatocytes / metabolism*
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Hepatocytes / virology
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Host Microbial Interactions / genetics*
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Host Microbial Interactions / physiology
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Humans
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Latent Infection / physiopathology
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Liver / pathology
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Liver / virology
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Primary Cell Culture
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Single-Cell Analysis
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Virus Replication / genetics
Substances
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DNA, Viral
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Guanine Nucleotide Exchange Factors
Grants and funding
The author(s) received specific funding for this work. This research was supported in part by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and by the Japan Agency for Medical Research and Development (AMED). In addition, this research was partially supported by the Program on the Innovative Development and the Application of New Drugs for Hepatitis B from AMED under Grant Number 20fk0310110.