Archives of Virology

, Volume 164, Issue 11, pp 2671–2682 | Cite as

Genomic and spatial variability of a European common vole hepevirus

  • René Ryll
  • Gerald Heckel
  • Victor M. Corman
  • Jan Felix DrexlerEmail author
  • Rainer G. UlrichEmail author
Original Article


Rodents host different orthohepeviruses, namely orthohepevirus C genotype HEV-C1 (rat hepatitis E virus, HEV) and the additional putative genotypes HEV-C3 and HEV-C4. Here, we screened 2,961 rodents from Central Europe by reverse transcription polymerase chain reaction (RT-PCR) and identified HEV RNA in 13 common voles (Microtus arvalis) and one bank vole (Myodes glareolus) with detection rates of 2% (95% confidence interval [CI]: 1-3.4) and 0.08% (95% CI: 0.002-0.46), respectively. Sequencing of a 279-nucleotide RT-PCR amplicon corresponding to a region within open reading frame (ORF) 1 showed a high degree of similarity to recently described common vole-associated HEV (cvHEV) sequences from Hungary. Five novel complete cvHEV genome sequences from Central Europe showed the typical HEV genome organization with ORF1, ORF2 and ORF3 and RNA secondary structure. Uncommon features included a noncanonical start codon in ORF3, multiple insertions and deletions within ORF1 and ORF2/ORF3, and the absence of a putative ORF4. Phylogenetic analysis showed all of the novel cvHEV sequences to be monophyletic, clustering most closely with an unassigned bird-derived sequence and other sequences of the species Orthohepevirus C. The nucleotide and amino acid sequence divergence of the common vole-derived sequences was significantly correlated with the spatial distance between the trapping sites, indicating mostly local evolutionary processes. Detection of closely related HEV sequences in common voles in multiple localities over a distance of 800 kilometers suggested that common voles are infected by cvHEV across broad geographic distances. The common vole-associated HEV strain is clearly divergent from HEV sequences recently found in narrow-headed voles (Microtus gregalis) and other cricetid rodents.



The authors thank Stephan Eichenberg for creating the map, and Filip Cierniak for helpful discussions.

Author contributions

RGU and JFD designed the study; RR and JFD performed the analyses; RR, VMC, JFD, GH and RGU wrote the manuscript. All authors approved the final version of the manuscript.

Compliance with ethical standards


This study was funded in part by the German Federal Ministry of Health (ZMVI1-2518FSB705) to VMC, by DZIF (TTU Emerging Infections, network RaBoPa) to RGU, and by the Swiss National Science Foundation (31003A-176209) to GH.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animal experiments performed by any of the authors.

Supplementary material

705_2019_4347_MOESM1_ESM.pdf (287 kb)
Supplementary material 1 (PDF 287 kb)
705_2019_4347_MOESM2_ESM.docx (25 kb)
Supplementary material 2 (DOCX 25 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Novel and Emerging Infectious DiseasesGreifswald-Insel RiemsGermany
  2. 2.University of Bern, Institute of Ecology and EvolutionBernSwitzerland
  3. 3.Swiss Institute of Bioinformatics, Quartier SorgeLausanneSwitzerland
  4. 4.Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of VirologyBerlinGermany
  5. 5.German Centre for Infection Research (DZIF), Associated Partner Site BerlinBerlinGermany
  6. 6.German Centre for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Insel RiemsGreifswald-Insel RiemsGermany

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