Mouse models of acute and chronic hepacivirus infection

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.

Source: ScienceNOW - July 13, 2017 Category: Science Authors: Billerbeck, E., Wolfisberg, R., Fahnoe, U., Xiao, J. W., Quirk, C., Luna, J. M., Cullen, J. M., Hartlage, A. S., Chiriboga, L., Ghoshal, K., Lipkin, W. I., Bukh, J., Scheel, T. K. H., Kapoor, A., Rice, C. M. Tags: Immunology, Microbiology reports Source Type: news