We analysed the influence of MHC class II and genes on Puumala virus (PUUV) infection in bank voles (). We considered voles sampled in five European localities or derived from a previous experiment that showed variable infection success of PUUV. The genetic variation observed in the and genes was assessed by using single-strand conformation polymorphism and pyrosequencing methods, respectively. Patterns were compared with those obtained from 13 microsatellites. We revealed significant genetic differentiation between PUUV-seronegative and -seropositive bank voles sampled in wild populations, at the gene only. The absence of genetic differentiation observed at neutral microsatellites confirmed the important role of selective pressures in shaping these patterns. Also, we found no significant associations between infection success and MHC alleles among laboratory-colonized bank voles, which is explained by a loss of genetic variability that occurred during the captivity of these voles.


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  1. Asikainen, K., Hanninen, T., Henttonen, H., Niemimaa, J., Laakkonen, J., Andersen, H., Bille, N., Leirs, H., Vaheri, A. & other authors(2000). Molecular evolution of Puumala hantavirus in Fennoscandia: phylogenetic analysis of strains from two recolonization routes, Karelia and Denmark. J Gen Virol 81, 2833–2841. [Google Scholar]
  2. Axtner, J. & Sommer, S.(2007). Gene duplication, allelic diversity, selection processes and adaptive value of MHC class II DRB genes of the bank vole, Clethrionomys glareolus. Immunogenetics 59, 417–426.[CrossRef] [Google Scholar]
  3. Bryja, J., Galan, M., Charbonnel, N. & Cosson, J. F.(2005). Analysis of MHC class II gene in voles using CE-SSCP. Mol Ecol Notes 5, 173–176.[CrossRef] [Google Scholar]
  4. Bryja, J., Galan, M., Charbonnel, N. & Cosson, J. F.(2006). Duplication, balancing selection and trans-species evolution explain the high levels of polymorphism of the DQA MHC class II gene in voles (Arvicolinae). Immunogenetics 58, 191–202.[CrossRef] [Google Scholar]
  5. Deter, J., Chaval, Y., Galan, M., Gauffre, B., Morand, S., Henttonen, H., Laakkonen, J., Voutilainen, L., Charbonnel, N. & other authors(2008a). Kinship, dispersal and hantavirus transmission in bank and common voles. Arch Virol 153, 435–444.[CrossRef] [Google Scholar]
  6. Deter, J., Chaval, Y., Galan, M., Henttonen, H., Laakkonen, J., Voutilainen, L., Ribas Salvador, A., Bryja, J., Morand, S. & other authors(2008b). Association between the DQA MHC class II gene and Puumala virus infection in the specific reservoir Myodes glareolus. Infect Genet Evol 8, 450–458.[CrossRef] [Google Scholar]
  7. Excoffier, L., Laval, G. & Schneider, S.(2005). Arlequin ver. 3.0: an integrated software package for population genetics data analysis. Evol Bioinform Online 1, 47–50. [Google Scholar]
  8. Galan, M., Guivier, E., Caraux, G., Charbonnel, N. & Cosson, J. F.(2010). A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies. BMC Genomics 11, 296.[CrossRef] [Google Scholar]
  9. Goudet, J.(2001).fstat, a program to estimate and test gene diversities and fixation indices (version 2.9.3). http://www2.unil.ch/popgen/softwares/fstat.htm.
  10. Haldane, J. B. S.(1956). The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet 20, 309–311.[CrossRef] [Google Scholar]
  11. Hall, T. A.(1999). BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41, 95–98. [Google Scholar]
  12. Hardestam, J., Karlsson, M., Falk, K. I., Olsson, G., Klingstrom, J. & Lundkvist, A.(2008). Puumala hantavirus excretion kinetics in bank voles. Emerg Infect Dis 14, 1209–1215.[CrossRef] [Google Scholar]
  13. Johansson, P., Olsson, G. E., Low, H. T., Bucht, G., Ahlm, C., Juto, P. & Elgh, F.(2008). Puumala hantavirus genetic variability in an endemic region (Northern Sweden). Infect Genet Evol 8, 286–296.[CrossRef] [Google Scholar]
  14. Jombart, T., Pontier, D. & Dufour, A. B.(2009). Genetic markers in the playground of multivariate analysis. Heredity 102, 330–341.[CrossRef] [Google Scholar]
  15. Kallio, E. R., Klingstrom, J., Gustafsson, E., Manni, T., Vaheri, A., Henttonen, H., Vapalahti, O. & Lundkvist, A.(2006). Prolonged survival of Puumala hantavirus outside the host: evidence for indirect transmission via the environment. J Gen Virol 87, 2127–2134.[CrossRef] [Google Scholar]
  16. Kallio, E. R., Voutilainen, L., Vapalahti, O., Vaheri, A., Henttonen, H., Koskela, E. & Mappes, T.(2007). Endemic hantavirus infection impairs the winter survival of its rodent host. Ecology 88, 1911–1916.[CrossRef] [Google Scholar]
  17. Kallio-Kokko, H., Laakkonen, J., Rizzoli, A., Tagliapietra, V., Cattadori, I., Perkins, S. E., Hudson, P. J., Cristofolini, A., Versini, W. & other authors(2006). Hantavirus and arenavirus antibody prevalence in rodents and humans in Trentino, Northern Italy. Epidemiol Infect 134, 830–836.[CrossRef] [Google Scholar]
  18. Klein, J., Bontrop, R. E., Dawkins, R. L., Erlich, H. A., Gyllensten, U. B., Heise, E. R., Jones, P. P., Parham, P., Wakeland, E. K. & other authors(1990). Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31, 217–219. [Google Scholar]
  19. Klein, S. L., Cernetich, A., Hilmer, S., Hoffman, E. P., Scott, A. L. & Glass, G. E.(2004). Differential expression of immunoregulatory genes in male and female Norway rats following infection with Seoul virus. J Med Virol 74, 180–190.[CrossRef] [Google Scholar]
  20. Lahdevirta, J.(1971). Nephropathia epidemica in Finland. A clinical histological and epidemiological study. Ann Clin Res 3, 1–54. [Google Scholar]
  21. Luikart, G., England, P. R., Tallmon, D., Jordan, S. & Taberlet, P.(2003). The power and promise of population genomics: from genotyping to genome typing. Nat Rev Genet 4, 981–994. [Google Scholar]
  22. Lundkvist, A. & Niklasson, B.(1992). Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins: identification of epitopes involved in neutralization. Arch Virol 126, 93–105.[CrossRef] [Google Scholar]
  23. Mäkelä, S., Mustonen, J., Ala-Houhala, I., Hurme, M., Partanen, J., Vapalahti, O., Vaheri, A. & Pasternack, A.(2002). Human leukocyte antigen–B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-α(-308) G/A polymorphism. J Infect Dis 186, 843–846.[CrossRef] [Google Scholar]
  24. Meyer, B. J. & Schmaljohn, C. S.(2000). Persistent hantavirus infections: characteristics and mechanisms. Trends Microbiol 8, 61–67.[CrossRef] [Google Scholar]
  25. Mustonen, J., Brummer-Korvenkontio, M., Hedman, K., Pasternack, A., Pietila, K. & Vaheri, A.(1994). Nephropathia epidemica in Finland: a retrospective study of 126 cases. Scand J Infect Dis 26, 7–13.[CrossRef] [Google Scholar]
  26. Mustonen, J., Partanen, J., Kanerva, M., Pietilä, K., Vapalahti, O., Pasternack, A. & Vaheri, A.(1996). Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus. Kidney Int 49, 217–221.[CrossRef] [Google Scholar]
  27. Olsson, G. E., White, N., Ahlm, C., Elgh, F., Verlemyr, A. C., Juto, P. & Palo, R. T.(2002). Demographic factors associated with hantavirus infection in bank voles (Clethrionomys glareolus). Emerg Infect Dis 8, 924–929.[CrossRef] [Google Scholar]
  28. Plyusnin, A., Horling, J., Kanerva, M., Mustonen, J., Cheng, Y., Partanen, J., Vapalahti, O., Kukkonen, S. K., Niemimaa, J. & other authors(1997). Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents. J Clin Microbiol 35, 1090–1096. [Google Scholar]
  29. Raymond, M. & Rousset, F.(1995).genepop (version 1.2): population genetics software for exact tests and ecumenicism. J Hered 86, 248–249. [Google Scholar]
  30. Rikalainen, K., Graputto, A., Knott, E., Koskela, E. & Mappes, T.(2008). A large panel of novel microsatellite markers for the bank vole (Myodes glareolus). Mol Ecol Resour 8, 1164–1168.[CrossRef] [Google Scholar]
  31. Schad, J., Ganzhorn, J. U. & Sommer, S.(2005). Parasite burden and constitution of major histocompatibility complex in the Malagasy mouse lemur, Microcebus murinus. Evolution 59, 439–450.[CrossRef] [Google Scholar]
  32. Sironen, T., Kallio, E. R., Vaheri, A., Lundkvist, A. & Plyusnin, A.(2008). Quasispecies dynamics and fixation of a synonymous mutation in hantavirus transmission. J Gen Virol 89, 1309–1313.[CrossRef] [Google Scholar]
  33. Spurgin, L. G. & Richardson, D. S.(2010). How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc Biol Sci 277, 979–988.[CrossRef] [Google Scholar]
  34. Tamura, K., Dudley, J., Nei, M. & Kumar, S.(2007).mega4: molecular evolutionary genetics analysis (mega) software version 4.0. Mol Biol Evol 24, 1596–1599.[CrossRef] [Google Scholar]
  35. Terajima, M., Vapalahti, O., Van Epps, H. L., Vaheri, A. & Ennis, F. A.(2004). Immune responses to Puumala virus infection and the pathogenesis of nephropathia epidemica. Microbes Infect 6, 238–245.[CrossRef] [Google Scholar]
  36. Thioulouse, J., Chessel, D., Dole'dec, S. & Olivier, J. M.(1997).ade-4: a multivariate analysis and graphical display software. Stat Comput 7, 75–83.[CrossRef] [Google Scholar]
  37. Vapalahti, O., Mustonen, J., Lundkvist, A., Henttonen, H., Plyusnin, A. & Vaheri, A.(2003). Hantavirus infections in Europe. Lancet Infect Dis 3, 653–661.[CrossRef] [Google Scholar]
  38. Yanagihara, R., Amyx, H. L. & Gajdusek, D. C.(1985). Experimental infection with Puumala virus, the etiologic agent of nephropathia epidemica, in bank voles (Clethrionomys glareolus). J Virol 55, 34–38. [Google Scholar]

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vol. , part 10, pp. 2507–2512

Sample size, number of PUUV-infected voles, sex and genetic diversity for five localities and for the S1 experimental dataset

Detailed information concerning the experimental infection datasets used in this study

Neighbour-joining phylogeny for 39 sequences of the -exon2 gene from our dataset

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