Evidence for Novel Hepaciviruses in Rodents

Drexler, Jan Felix; Corman, Victor Max; Müller, Marcel Alexander; Lukashev, Alexander N.; Gmyl, Anatoly; Coutard, Bruno; Adam, Alexander; Ritz, Daniel; Leijten, Lonneke M.; van Riel, Debby; Kallies, Rene; Klose, Stefan M.; Gloza-Rausch, Florian; Binger, Tabea; Annan, Augustina; Adu-Sarkodie, Yaw; Oppong, Samuel; Bourgarel, Mathieu; Rupp, Daniel; Hoffmann, Bernd; Schlegel, Mathias; Kümmerer, Beate M.; Krüger, Detlev H.; Schmidt-Chanasit, Jonas; Setién, Alvaro Aguilar; Cottontail, Veronika M.; Hemachudha, Thiravat; Wacharapluesadee, Supaporn; Osterrieder, Klaus; Bartenschlager, Ralf; Matthee, Sonja; Beer, Martin; Kuiken, Thijs; Reusken, Chantal; Leroy, Eric M.; Ulrich, Rainer G.; Drosten, Christian

Hepatitis C virus is one of the leading causes of human morbidity and mortality due to hepatitis, liver cirrhosis, and hepatocellular carcinoma [1, 2, 3] . It has become the main reason for liver transplantation in developed countries and represents an economic burden exceeding 1 billion US$ of direct health costs [4, 5] . New estimates of the burden of disease suggest at least 185 million individuals worldwide to have been seropositive in 2005, with a tendency to increase [6] . Treatment has considerably improved due to the optimization of antiviral regimens and the advent of new antiviral drugs [7, 8, 9] . However, treatment in resource-limited settings is hardly accessible [10] . The most effective instrument to prevent new infections with HCV would be a prophylactic vaccine. Unfortunately, chimpanzees are the only known animal species to adequately reflect human HCV infection [11] . Vaccine development is hampered by the lack of a small animal model accessible at early stages of vaccine development [12, 13] . Mice cannot be infected with HCV [14] , but rats and mice engrafted with human hepatoma cells or transgenic for human CD81 and other co-receptor molecules have been proposed [12, 15, 16, 17] . Mouse-adapted HCV has also been generated [16, 18] . Still, these models are highly demanding from a technical point of view and reflect only parts of the pathogenesis and lifecycle of HCV, precluding their wide application [12, 19] .