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Evidence for Novel Hepaciviruses in Rodents

Jan Felix Drexler 1 Victor Max Corman 2 Marcel Alexander Müller 2 Alexander Lukashev 3 Anatoly Gmyl 3 Bruno Coutard 4 Alexander Adam 5 Daniel Ritz 1 Lonneke Leijten 6 Debby van Riel 6 René Kallies 2 Stefan Klose 7 Florian Gloza-Rausch 2 Tabea Binger 2 Augustina Annan 8 Yaw Adu-Sarkodie 9 Samuel Oppong 9 Mathieu Bourgarel 10 Daniel Rupp 11 Bernd Hoffmann 12 Mathias Schlegel 13 Beate Kümmerer 1 Detlev Krüger 14 Jonas Schmidt-Chanasit 15 Alvaro Aguilar Setién 16 Veronika Cottontail 7 Thiravat Hemachudha 17 Supaporn Wacharapluesadee 17 Klaus Osterrieder 18 Ralf Bartenschlager 19 Sonja Matthee 20 Martin Beer 21 Thijs Kuiken 22 Chantal Reusken 23 Eric Leroy 24, 25 Rainer Ulrich 13 Christian Drosten 26
Abstract : Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.
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Jan Felix Drexler, Victor Max Corman, Marcel Alexander Müller, Alexander Lukashev, Anatoly Gmyl, et al.. Evidence for Novel Hepaciviruses in Rodents. PLoS Pathogens, Public Library of Science, 2013, 9 (6), pp.e1003438. ⟨10.1371/journal.ppat.1003438⟩. ⟨hal-02395310⟩



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