Evidence for novel hepaciviruses in rodents.
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 insig...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:9d69d55584884b4f8a36a3eb0a8044b12021-11-18T06:05:30ZEvidence for novel hepaciviruses in rodents.1553-73661553-737410.1371/journal.ppat.1003438https://doaj.org/article/9d69d55584884b4f8a36a3eb0a8044b12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23818848/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis 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.Jan Felix DrexlerVictor Max CormanMarcel Alexander MüllerAlexander N LukashevAnatoly GmylBruno CoutardAlexander AdamDaniel RitzLonneke M LeijtenDebby van RielRene KalliesStefan M KloseFlorian Gloza-RauschTabea BingerAugustina AnnanYaw Adu-SarkodieSamuel OppongMathieu BourgarelDaniel RuppBernd HoffmannMathias SchlegelBeate M KümmererDetlev H KrügerJonas Schmidt-ChanasitAlvaro Aguilar SetiénVeronika M CottontailThiravat HemachudhaSupaporn WacharapluesadeeKlaus OsterriederRalf BartenschlagerSonja MattheeMartin BeerThijs KuikenChantal ReuskenEric M LeroyRainer G UlrichChristian DrostenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 6, p e1003438 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jan Felix Drexler Victor Max Corman Marcel Alexander Müller Alexander N Lukashev Anatoly Gmyl Bruno Coutard Alexander Adam Daniel Ritz Lonneke M Leijten Debby van Riel Rene Kallies Stefan M Klose Florian Gloza-Rausch Tabea Binger Augustina Annan Yaw Adu-Sarkodie Samuel Oppong Mathieu Bourgarel Daniel Rupp Bernd Hoffmann Mathias Schlegel Beate M Kümmerer Detlev H Krüger Jonas Schmidt-Chanasit Alvaro Aguilar Setién Veronika M Cottontail Thiravat Hemachudha Supaporn Wacharapluesadee Klaus Osterrieder Ralf Bartenschlager Sonja Matthee Martin Beer Thijs Kuiken Chantal Reusken Eric M Leroy Rainer G Ulrich Christian Drosten Evidence for novel hepaciviruses in rodents. |
| description |
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. |
| format |
article |
| author |
Jan Felix Drexler Victor Max Corman Marcel Alexander Müller Alexander N Lukashev Anatoly Gmyl Bruno Coutard Alexander Adam Daniel Ritz Lonneke M Leijten Debby van Riel Rene Kallies Stefan M Klose Florian Gloza-Rausch Tabea Binger Augustina Annan Yaw Adu-Sarkodie Samuel Oppong Mathieu Bourgarel Daniel Rupp Bernd Hoffmann Mathias Schlegel Beate M Kümmerer Detlev H Krüger Jonas Schmidt-Chanasit Alvaro Aguilar Setién Veronika M Cottontail Thiravat Hemachudha Supaporn Wacharapluesadee Klaus Osterrieder Ralf Bartenschlager Sonja Matthee Martin Beer Thijs Kuiken Chantal Reusken Eric M Leroy Rainer G Ulrich Christian Drosten |
| author_facet |
Jan Felix Drexler Victor Max Corman Marcel Alexander Müller Alexander N Lukashev Anatoly Gmyl Bruno Coutard Alexander Adam Daniel Ritz Lonneke M Leijten Debby van Riel Rene Kallies Stefan M Klose Florian Gloza-Rausch Tabea Binger Augustina Annan Yaw Adu-Sarkodie Samuel Oppong Mathieu Bourgarel Daniel Rupp Bernd Hoffmann Mathias Schlegel Beate M Kümmerer Detlev H Krüger Jonas Schmidt-Chanasit Alvaro Aguilar Setién Veronika M Cottontail Thiravat Hemachudha Supaporn Wacharapluesadee Klaus Osterrieder Ralf Bartenschlager Sonja Matthee Martin Beer Thijs Kuiken Chantal Reusken Eric M Leroy Rainer G Ulrich Christian Drosten |
| author_sort |
Jan Felix Drexler |
| title |
Evidence for novel hepaciviruses in rodents. |
| title_short |
Evidence for novel hepaciviruses in rodents. |
| title_full |
Evidence for novel hepaciviruses in rodents. |
| title_fullStr |
Evidence for novel hepaciviruses in rodents. |
| title_full_unstemmed |
Evidence for novel hepaciviruses in rodents. |
| title_sort |
evidence for novel hepaciviruses in rodents. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9d69d55584884b4f8a36a3eb0a8044b1 |
| work_keys_str_mv |
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