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Phylogenetic analysis of Puumala virus subtype Bavaria, characterization and diagnostic use of its recombinant nucleocapsid protein

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Abstract

Puumala virus (PUUV) is the predominant hantavirus species in Germany causing large numbers of mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS). During an outbreak in South-East Germany in 2004 a novel PUUV subtype designated Bavaria was identified as the causative agent of HFRS in humans [1]. Here we present a molecular characterization of this PUUV strain by investigating novel partial and almost entire nucleocapsid (N) protein-encoding small (S-) segment sequences and partial medium (M-) segment sequences from bank voles (Myodes glareolus) trapped in Lower Bavaria during 2004 and 2005. Phylogenetic analyses confirmed their classification as subtype Bavaria, which is further subdivided into four geographical clusters. The entire N protein, harbouring an amino-terminal hexahistidine tag, of the Bavarian strain was produced in yeast Saccharomyces cerevisiae and showed a slightly different reactivity with N-specific monoclonal antibodies, compared to the yeast-expressed N protein of the PUUV strain Vranica/Hällnäs. Endpoint titration of human sera from different parts of Germany and from Finland revealed only very slight differences in the diagnostic value of the different recombinant proteins. Based on the novel N antigen indirect and monoclonal antibody capture IgG-ELISAs were established. By using serum panels from Germany and Finland their validation demonstrated a high sensitivity and specificity. In summary, our investigations demonstrated the Bavarian PUUV strain to be genetically divergent from other PUUV strains and the potential of its N protein for diagnostic applications.

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Acknowledgements

We would like to thank Ausra Razanskiene and Kestutis Sasnauskas (Vilnius) and Bernd Köllner (Riems) for continous support and helpful discussions, Åke Lundkvist (Stockholm), Kumiko Yoshimatsu and Jiro Arikawa (Sapporo) for provision of N protein-specific mAbs and Olli Vapalahti (Helsinki), Regina Allwinn and Holger F. Rabenau (Frankfurt) for provision of human serum panels. We kindly acknowledge Harald Weber, Aileene Lorber, Rahime Terzioglu, Elmar Schröpfer, Ralf Hagen, Mirko Köhler, Anne Grumbach, Peter Klein and Kerstin Weiss for their support during rodent trapping, rodent necropsy and collection of human sera in South-East Germany. The excellent technical lab assistance of Jana Blumhardt, Ina Römer, Dörte Kaufmann, Sabine Fink and Astrid Thomas is gratefully acknowledged. The work was supported by Research-Project M/SAB1/5/A017 for the Bundeswehr Medical Service to RGU.

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Authors and Affiliations

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

    Marc Mertens, Martin H. Groschup & Rainer G. Ulrich

  2. Computational and Molecular Population Genetics (CMPG), Institute of Ecology and Evolution, University of Bern, 3012, Bern, Switzerland

    Eveline Kindler & Gerald Heckel

  3. Diagnostic Virology Laboratory, Bernhard-Nocht-Institute for Tropical Medicine, 20359, Hamburg, Germany

    Petra Emmerich & Jonas Schmidt-Chanasit

  4. Labor Enzenauer und Kollegen, Abteilung Serologie, 49088, Osnabrück, Germany

    Jutta Esser

  5. Landesgesundheitsamt Baden-Württemberg, Regierungspräsidium Stuttgart, 70191, Stuttgart, Germany

    Christiane Wagner-Wiening

  6. Department of Medical Bioreconnaissance and Verification, Bundeswehr Institute of Microbiology, Neuherbergstr. 11, 80937, Munich, Germany

    Roman Wölfel

  7. VU Institute of Biotechnology, 02241, Vilnius, Lithuania

    Rasa Petraityte-Burneikiene & Aurelija Zvirbliene

  8. Department of Virology & Rickettsiology, Bundeswehr Institute of Microbiology, Neuherbergstr. 11, 80937, Munich, Germany

    Gerhard Dobler & Sandra S. Essbauer

  9. Institute of Animal Hygiene and Veterinary Public Health, Veterinary Faculty, University of Leipzig, 04103, Leipzig, Germany

    Martin Pfeffer

  10. Swiss Institute of Bioinformatics (SIB), 1015, Lausanne, Switzerland

    Gerald Heckel

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  1. Marc Mertens
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Correspondence to Sandra S. Essbauer.

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Marc Mertens and Eveline Kindler contributed equally to this paper.

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11262_2011_620_MOESM1_ESM.pptx

Supplementary Figure. Bayesian reconstruction of phylogenetic relationships based on 968 bp mtDNA (cyt b) from 120 Myodes glareolus with M. rufocanus as outgroup. Only support values for main nodes that connect major evolutionary lineages are displayed. Posterior probabilities are indicated above the major branches and percentage of bootstrap support for neighbour-joining (NJ) algorithms below the branches. * indicates a different topology based on NJ algorithms, ns refers to posterior probabilities <0.50 and percentages of bootstrap support <50%. Arrows depict cyt b sequences from bank voles from Bavaria where PUUV sequences were detected in (PPTX 64 kb)

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Mertens, M., Kindler, E., Emmerich, P. et al. Phylogenetic analysis of Puumala virus subtype Bavaria, characterization and diagnostic use of its recombinant nucleocapsid protein. Virus Genes 43, 177–191 (2011). https://doi.org/10.1007/s11262-011-0620-x

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  • DOI: https://doi.org/10.1007/s11262-011-0620-x

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