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Genomic and spatial variability of a European common vole hepevirus

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Abstract

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.

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Acknowledgements

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

Author information

Authors and Affiliations

  1. Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Novel and Emerging Infectious Diseases, Südufer 10, 17493, Greifswald-Insel Riems, Germany

    René Ryll & Rainer G. Ulrich

  2. University of Bern, Institute of Ecology and Evolution, Bern, Switzerland

    Gerald Heckel

  3. Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Genopode, Lausanne, Switzerland

    Gerald Heckel

  4. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Campus Charité Mitte, Charitéplatz 1, 10098, Berlin, Germany

    Victor M. Corman & Jan Felix Drexler

  5. German Centre for Infection Research (DZIF), Associated Partner Site Berlin, Berlin, Germany

    Victor M. Corman & Jan Felix Drexler

  6. German Centre for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Insel Riems, Greifswald-Insel Riems, Germany

    Rainer G. Ulrich

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  1. René Ryll
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  2. Gerald Heckel
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  3. Victor M. Corman
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  4. Jan Felix Drexler
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  5. Rainer G. Ulrich
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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.

Corresponding authors

Correspondence to Jan Felix Drexler or Rainer G. Ulrich.

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Funding

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.

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Ryll, R., Heckel, G., Corman, V.M. et al. Genomic and spatial variability of a European common vole hepevirus. Arch Virol 164, 2671–2682 (2019). https://doi.org/10.1007/s00705-019-04347-1

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