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. 2022 Feb 8;12:2133. doi: 10.1038/s41598-022-05882-9

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Kinetics of intrahepatic cccDNA in the chimeric mice during ETV treatment. (A) Schematic representation of the experiment. All six chimeric mice undergoing hepatocyte repopulation were inoculated with HBV. The two mice were treated with ETV (0.2 mg/kg/day) for 4 weeks and then followed for another 2 weeks after ETV withdrawal. The other two mice were treated with saline to serve as controls. (B) The serum HBV-DNA levels, (C) serum HBsAg levels, (D) serum HBcrAg levels, (E) human serum albumin and (F) their body weights were monitored during and after ETV treatment. Southern blot analysis of (G) HBV-DNA (rcDNA and ssDNA) and (H) cccDNA in the livers of HBV-infected chimeric mice, with or without ETV treatment, on week 10. The images of full length (G and H) were provided in Fig. S5 (A and B). These serum data (B, C and D) were associated with the levels of HBV-DNA replicative intermediates (rcDNA and ssDNA) and cccDNA in the livers of the ETV-treated and control groups by SB. (I) The intrahepatic cccDNA level of each chimeric mouse was determined by ddPCR. (J) Intrahepatic hRPP30 levels were determined by ddPCR. (K) Intrahepatic cccDNA levels/cell were calculated for each mouse. Values and error bars represent the means and standard deviations of two or more independent experiments. The images of the full-length membrane, with the edge of the membrane visible was provided in the original images of the supplemental information file.