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J Gen Virol. 2017 May;98(5):1040-1047. doi: 10.1099/jgv.0.000726. Epub 2017 May 25.

Usefulness of humanized cDNA-uPA/SCID mice for the study of hepatitis B virus and hepatitis C virus virology.

Author information

1
1​Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan 2​Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
2
2​Liver Research Project Center, Hiroshima University, Hiroshima, Japan 3​Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
3
2​Liver Research Project Center, Hiroshima University, Hiroshima, Japan 4​PhoenixBio Co., Ltd, Higashihiroshima, Japan.
4
2​Liver Research Project Center, Hiroshima University, Hiroshima, Japan 1​Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan 3​Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.

Abstract

Urokinase-type plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice transplanted with human hepatocytes are permissive for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. However, one of the problems affecting uPA transgenic mice is the expansion of mouse hepatocyte colonies due to homologous recombination of the uPA gene. In this study, we attempted to infect HBV and HCV in humanized cDNA-uPA/SCID mice, a novel uPA transgenic mouse model designed to overcome this disadvantage. Three hundred and eighty-six uPA/SCID and 493 cDNA-uPA/SCID mice were transplanted with human hepatocytes and then injected with either HBV- or HCV-positive human serum samples or HBV-transfected cell culture medium. Twelve weeks after human hepatocyte transplantation, the mouse serum concentration of human albumin, which is correlated with the degree of repopulation by human hepatocytes, was significantly higher in cDNA-uPA/SCID mice compared with uPA/SCID mice. HBV-infected cDNA-uPA/SCID mice showed significantly greater and more persistent viraemia, and similar virological effects by entecavir treatment were achieved in both systems. HCV-infected cDNA-uPA/SCID mice developed more frequent and significantly higher viraemia compared with uPA/SCID mice. The present study using a large number of mice showed that cDNA-uPA/SCID mice transplanted with human hepatocytes developed high and long-term persistent viraemia following HBV and HCV infection, and a higher survival rate was observed in cDNA-uPA/SCID compared with uPA/SCID mice. These mice may be a useful animal model for the study of HBV and HCV virology and the analysis of the effect of antiviral drugs.

PMID:
28141486
DOI:
10.1099/jgv.0.000726
[Indexed for MEDLINE]

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