4.6 Article

DOCK11 and DENND2A play pivotal roles in the maintenance of hepatitis B virus in host cells

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PLOS ONE
卷 16, 期 2, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0246313

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资金

  1. 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)
  2. Japan Agency for Medical Research and Development (AMED)
  3. Program on the Innovative Development and the Application of New Drugs for Hepatitis B from AMED [20fk0310110]

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Using single-cell RNA sequencing analysis, four genes including DOCK11 and DENND2A were identified to be linked to the maintenance of HBV in liver cells. Knockdown of these genes in primary human hepatocytes infected with HBV resulted in a decrease in both HBV DNA and covalently closed circular DNA. This study reveals a role for DOCK11 and DENND2A in maintaining HBV in a latent state.
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.

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