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A genetically humanized mouse model for hepatitis C virus infection.

ABSTRACT: Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo.

SUBMITTER: Dorner M

PROVIDER: S-EPMC3159410 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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A genetically humanized mouse model for hepatitis C virus infection.

Dorner Marcus M Dorner Marcus M Horwitz Joshua A JA Robbins Justin B JB Barry Walter T WT Feng Qian Q Mu Kathy K Jones Christopher T CT Schoggins John W JW Catanese Maria Teresa MT Burton Dennis R DR Law Mansun M Rice Charles M CM Ploss Alexander A

Nature 20110608 7350

Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mo ...[more]

PMID: 21654804

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A genetically humanized mouse model for hepatitis C virus infection.

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A genetically humanized mouse model for hepatitis C virus infection.

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