Molecular Determinants of Mouse Adaptation of Rat Hepacivirus
Raphael Wolfisberg, Kenn Holmbeck, Eva Billerbeck, Caroline E. Thorselius, Mariana N. Batista, Ulrik Fahnøe, Emma A. Lundsgaard, Matthew J. Kennedy, Louise Nielsen, Charles M. Rice, Jens Bukh, Troels K. H. Scheel
Abstract
A prophylactic vaccine is required to achieve the World Health Organization's objective for hepatitis C virus elimination as a serious public health threat. However, the lack of robust immunocompetent animal models supporting hepatitis C virus infection impedes vaccine development as well as studies of immune responses and viral evasion. Hepatitis C virus-related hepaciviruses were discovered in a number of animal species and provide useful surrogate infection models. Norway rat hepacivirus is of particular interest, as it enables studies in rats, an immunocompetent and widely used small laboratory animal model. Its adaptation to robust infection also in laboratory mice provides access to a broader set of mouse genetic lines and comprehensive research tools. The presented mouse-adapted infectious clones will be of utility for reverse genetic studies, and the Norway rat hepacivirus mouse model will facilitate studies of hepacivirus infection for in-depth characterization of virus-host interactions, immune responses, and liver pathology.