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. 2019 Jan 30;68(11):2044–2056. doi: 10.1136/gutjnl-2018-316091

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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Establishment of sustained HBV infection in human bone marrow mesenchymal stem cell-Fah^-/- Rag2^-/- IL-2Rγc^-/- SCID (hBMSC-FRGS) mice. (A) Serum human albumin (hALB) (grey columns), HBV DNA (black lines), (B) hepatitis B surface antigen (HBsAg) (grey columns) and hepatitis B e antigen (HBeAg) (black lines) levels in hBMSC-FRGS mice inoculated with HBV (genotype C) from 0 to 56 weeks postinfection (w.p.i.) (n=8/group). (C) Immunohistochemistry (IHC) staining for hALB⁺, HBsAg⁺ and HBcAg⁺ cells of liver tissues collected from HBV-infected and uninfected hBMSC-FRGS mice and FRGS mice at 16 w.p.i. (bar=200 µm). (D) Statistical analysis of IHC images to determine the proportion of HBsAg⁺ cells in the population of hALB⁺ cells from 0 to 56 w.p.i. (n=8/group). (E) Fluorescence in situ hybridisation (FISH) analysis for HBV DNA in the population of hALB⁺ cells collected from HBV-infected hBMSC-FRGS mice and uninfected controls at 4 w.p.i. (bar=20 µm). Detection of intrahepatic HBV covalently closed circular DNA (cccDNA) levels in HBV-infected hBMSC-FRGS mice from 0 to 56 w.p.i. by (F) Southern blot and (G) quantitative reverse transcription PCR (qRT-PCR) (n=8/group). (H) Analysis of the correlation between the serum HBV DNA and serum HBsAg levels and the correlation between the serum HBV DNA and intracellular HBV cccDNA levels (n=10). PEIU, Paul Ehrlich Institute units.