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

Within the genus, phylogeny suggests early divergence of ancestral rodent viruses from a lineage leading up to HCV and canine/equine hepaciviruses. Weakness of resolution in deep bifurcations of the NS3 gene phylogeny and lack of any highly significant preference for deep topological hypotheses in the NS5B gene phylogeny underline the ancestral origin of these viruses. Within the current dataset we can consider them equidistant from HCV and the canine/equine hepaciviruses, suggesting existence of independent taxonomic entities. HCV is one viral species whose genotypes are separated by more than 30% genomic nucleotide distance [67] , which corresponds to about 22-31% AA distance. Different species within the related sister genus Pegivirus, such as GBV-C and GBV-A, are separated from each other by about 45% AA distance [68] . Within the Genus Flavivirus, well-defined species such as dengue virus 1, West Nile virus, yellow fever virus and tickborne encephalitis virus are separated from each other by 48-60% AA distance. Comparing these values we could putatively assume that both Myodes-associated clades distant from each other by 70% AA sequence, as well as the Rhabdomys-associated clade separated from both of the aforementioned by 66-69% AA sequence, might form three distinct species. The canine/equine hepacivirus clade separated from HCV by 52-53% AA sequence would then also form a separate species. Furthermore, all rodent hepacivirus clades and specifically M. glareolus hepacivirus clade 2 were slightly more related to GBV-B than to HCV. GBV-B causes hepatitis in experimentally infected New World primates but not in humans and chimpanzees [61] . The true host of this virus is unknown, but our findings suggest that GBV-B might originate from rodents. Nevertheless, the genetic distance of GBV-B even to its closest relative, the Myodes hepacivirus clade 2 (63% AA sequence), suggests GBV-B to remain a solitary representative of a separate species of hepaciviruses.