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Science. 2017 Jul 14;357(6347):204-208. doi: 10.1126/science.aal1962.

Mouse models of acute and chronic hepacivirus infection.

Author information

1
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
2
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
3
College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
4
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, Ohio State University, Columbus, OH, USA.
5
Department of Pathology, New York University Medical Center, New York, NY, USA.
6
Department of Pathology, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
7
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
8
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA. ricec@rockefeller.edu.

Abstract

An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury. Transient depletion of CD4+ T cells before infection resulted in chronic infection, characterized by high levels of intrahepatic regulatory T cells and expression of inhibitory molecules on intrahepatic CD8+ T cells. Natural killer cells controlled early infection but were not essential for viral clearance. This model may provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines.

PMID:
28706073
PMCID:
PMC5654634
DOI:
10.1126/science.aal1962
[Indexed for MEDLINE]
Free PMC Article

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