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A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease.

ABSTRACT: Studies of hepatitis C virus (HCV) infection, immunopathogenesis, and resulting liver diseases have been hampered by the lack of a small animal model. We developed humanized mice with human immune system and liver tissues to improve the studies of hepatitis C virus pathogenesis and treatment.To promote engraftment of human hepatocytes, we expressed a fusion protein of the FK506 binding protein (FKBP) and caspase 8 under control of the albumin promoter (AFC8), which induces liver cell death, in Balb/C Rag2(-/-) ?C-null mice. Cotransplantation of human CD34(+) human hematopoietic stem cells (HSC) and hepatocyte progenitors into the transgenic mice led to efficient engraftment of human leukocytes and hepatocytes. We then infected these humanized mice (AFC8-hu HSC/Hep) with primary HCV isolates and studied HCV-induced immune responses and liver diseases.AFC8-hu HSC/Hep mice supported HCV infection in the liver and generated a human immune T-cell response against HCV. HCV infection induced liver inflammation, hepatitis, and fibrosis, which correlated with activation of stellate cells and expression of human fibrogenic genes.AFC8-hu HSC/Hep mice are a useful model of HCV infection, the immune response, and liver disease because they contain human immune system and liver cells. These mice become infected with HCV, generate a specific immune response against the virus, and develop liver diseases that include hepatitis and fibrosis. This model might also be used to develop therapeutics for HCV infection.

SUBMITTER: Washburn ML

PROVIDER: S-EPMC3066273 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease.

Washburn Michael L ML Bility Moses T MT Zhang Liguo L Kovalev Grigoriy I GI Buntzman Adam A Frelinger Jeffery A JA Barry Walter W Ploss Alexander A Rice Charles M CM Su Lishan L

Gastroenterology 20110113 4

<h4>Background & aims</h4>Studies of hepatitis C virus (HCV) infection, immunopathogenesis, and resulting liver diseases have been hampered by the lack of a small animal model. We developed humanized mice with human immune system and liver tissues to improve the studies of hepatitis C virus pathogenesis and treatment.<h4>Methods</h4>To promote engraftment of human hepatocytes, we expressed a fusion protein of the FK506 binding protein (FKBP) and caspase 8 under control of the albumin promoter (A ...[more]

PMID: 21237170

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A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease.

Publications

A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease.

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