Evidence for Novel Hepaciviruses in Rodents

PLoS Pathogens

Alexander Adam¹  Veronika M. Cottontail²  Christian Drosten³  Bernd Hoffmann⁴  Klaus Osterrieder⁵  Ralf Bartenschlager⁵  Alexander N. Lukashev⁶  Anatoly Gmyl⁶  Thijs Kuiken⁷  Martin Beer⁸  Mathias Schlegel⁸  Debby van Riel⁹  Eric M. Leroy⁹  Rene Kallies⁹  Detlev H. Krüger^1,10  Beate M. Kümmerer^1,11  Chantal Reusken^1,11  Supaporn Wacharapluesadee^1,12  Florian Gloza-Rausch^1,12  Alvaro Aguilar Setién^1,13  Daniel Ritz^1,14  Sonja Matthee^1,15  Victor Max Corman^1,16  Stefan M. Klose^1,16  Yaw Adu-Sarkodie^1,16  Jonas Schmidt-Chanasit^1,16  Marcel Alexander Müller^1,16  Lonneke M. Leijten^1,16  Jan Felix Drexler^1,16  Tabea Binger^1,16  Samuel Oppong^1,17  Daniel Rupp^1,18  Mathieu Bourgarel^1,18  Bruno Coutard^1,19  Rainer G. Ulrich^2,20  Augustina Annan^2,21  Thiravat Hemachudha^2,22 

[1] Architectures et Fonctions des Macromolécules Biologiques, UMR 7257 CNRS and Aix-Marseille University, Marseille, France;Bernhard Nocht Institute for Tropical Medicine, Department of Virology, Hamburg, Germany;Centre International de Recherches Médicales de Franceville, Franceville, Gabon;Centre de Cooperation Internationale de Recherche en Agronomie pour le Développement, UPR AGIRs, Montpellier, France;Chulalongkorn University, Faculty of Medicine, Neuroscience Center for Research and Development, Bangkok, Thailand;Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia;Department of Conservation Ecology and Entomology, Stellenbosch University, Stellenbosch, South Africa;Department of Infectious Diseases, Molecular Virology, Medical Facility, Heidelberg University, Heidelberg, Germany;Erasmus MC, Department of Viroscience, Rotterdam, The Netherlands;Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Greifswald–Insel Riems, Germany;Friedrich-Loeffler-Institut, Institute for Virus Diagnostics, Greifswald–Insel Riems, Germany;Institute of Experimental Ecology, University of Ulm, Ulm, Germany;Institute of Medical Virology (Helmut Ruska Haus), Charité Medical School, Berlin, Germany;Institute of Pathology, University of Cologne Medical Centre, Cologne, Germany;Institute of Virology, Free University of Berlin, Department of Veterinary Medicine, Berlin, Germany;Institute of Virology, University of Bonn Medical Centre, Bonn, Germany;Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana;Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;Lomonosov Moscow State University, Moscow, Russia;Netherlands Center for Infectious Disease Control, Bilthoven, The Netherlands;Noctalis, Centre for Bat Protection and Information, Bad Segeberg, Germany;Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, México DF, Mexico

关键词: Rodents;    Hepacivirus;    Hepatitis C virus;    Voles;    Bats;    Antibodies;    Dogs;    Phylogenetic analysis;   

DOI  :  10.1371/journal.ppat.1003438

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY