1887

Abstract

Puumala hantavirus (PUUV) is a rodent-borne agent causing nephropathia epidemica in humans, a milder form of haemorrhagic fever with renal syndrome occurring in Fennoscandia, central Europe and western Russia. In this study we characterized the immunogenicity of an -expressed nucleocapsid (N) protein of PUUV (strain Kazan-E6) in inbred mice (BALB/c, CBA and C57/BL6). The recombinant N (rN) protein raised PUUV-specific antibodies in all three tested murine haplotypes, and all IgG subclasses were detected. Epitope mapping using peptides spanning the N protein revealed that the B-cell recognition sites were mainly located at the amino-terminal part of the protein. Proliferative T-helper (Th) lymphocyte responses were detected in all haplotypes after a single immunization with rN. Several Th-recognition sites, spanning amino acids 6–27, 96–117, 211–232 and 256–277, were identified using overlapping peptides. Peptides representing the identified sites could also prime Th-lymphocytes to proliferate in response to recall with rN protein, thereby confirming the authenticity of the identified sites. The rN-primed Th-lymphocytes produced predominantly interleukin (IL)-2 and gamma interferon, together with lower levels of IL-4 and IL-6, indicating a mixed Th1/Th2 response.

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2001-01-01
2019-12-11
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References

  1. Antoniadis, A., Stylianakis, A., Papa, A., Alexiou-Daniel, S., Lampropoulos, A., Nichol, S. T., Peters, C. J. & Spiropoulou, C. F. ( 1996; ). Direct genetic detection of Dobrava virus in Greek and Albanian patients with hemorrhagic fever with renal syndrome. Journal of Infectious Diseases 174, 407-410.[CrossRef]
    [Google Scholar]
  2. Arikawa, J., Schmaljohn, A. L., Dalrymple, J. M. & Schmaljohn, C. S. ( 1989; ). Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. Journal of General Virology 70, 615-624.[CrossRef]
    [Google Scholar]
  3. Arikawa, J., Yao, J. S., Yoshimatsu, K., Takashima, I. & Hashimoto, N. ( 1992; ). Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies. Archives of Virology 126, 271-281.[CrossRef]
    [Google Scholar]
  4. Asada, H., Tamura, M., Kondo, K., Okuno, Y., Takahashi, Y., Dohi, Y., Nagai, T., Kurata, T. & Yamanishi, K. ( 1987; ). Role of T lymphocyte subsets in protection and recovery from Hantaan virus infection in mice. Journal of General Virology 68, 1961-1969.[CrossRef]
    [Google Scholar]
  5. Asada, H., Tamura, M., Kondo, K., Dohi, Y. & Yamanishi, K. ( 1988; ). Cell-mediated immunity to virus causing haemorrhagic fever with renal syndrome: generation of cytotoxic T lymphocytes. Journal of General Virology 69, 2179-2188.[CrossRef]
    [Google Scholar]
  6. Asada, H., Balachandra, K., Tamura, M., Kondo, K. & Yamanishi, K. ( 1989; ). Cross-reactive immunity among different serotypes of virus causing haemorrhagic fever with renal syndrome. Journal of General Virology 70, 819-825.[CrossRef]
    [Google Scholar]
  7. Brummer-Korvenkontio, M., Vaheri, A., Hovi, T., von Bonsdorff, C. H., Vuorimies, J., Manni, T., Penttinen, K., Oker-Blom, N. & Lahdevirta, J. ( 1980; ). Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection. Journal of Infectious Diseases 141, 131-134.[CrossRef]
    [Google Scholar]
  8. Chen, L. B. & Yang, W. S. ( 1990; ). Abnormalities of T cell immunoregulation in hemorrhagic fever with renal syndrome. Journal of Infectious Diseases 161, 1016-1019.[CrossRef]
    [Google Scholar]
  9. Dantas, J. R.Jr, Okuno, Y., Asada, H., Tamura, M., Takahashi, M., Tanishita, O., Takahashi, Y., Kurata, T. & Yamanishi, K. ( 1986; ). Characterization of glycoproteins of viruses causing hemorrhagic fever with renal syndrome (HFRS) using monoclonal antibodies. Virology 151, 379-384.[CrossRef]
    [Google Scholar]
  10. de Carvalho Nicacio, C., Lundkvist, Å., Brus Sjölander, K., Plyusnin, A., Salonen, E.-M. & Björling, E. ( 2000a; ). A neutralizing recombinant human antibody Fab fragment against Puumala hantavirus. Journal of Medical Virology 60, 446-454.[CrossRef]
    [Google Scholar]
  11. de Carvalho Nicacio, C., Björling, E. & Lundkvist, Å. ( 2000b; ). Immunoglobulin A responses to Puumala hantavirus. Journal of General Virology 81, 1453-1461.
    [Google Scholar]
  12. Elgh, F., Lundkvist, Å., Alexeyev, O. A., Wadell, G. & Juto, P. ( 1996; ). A major antigenic domain for the human humoral response to Puumala virus nucleocapsid protein is located at the amino-terminus. Journal of Virological Methods 59, 161-172.[CrossRef]
    [Google Scholar]
  13. Ennis, F. A., Cruz, J., Spiropoulou, C. F., Waite, D., Peters, C. J., Nichol, S. T., Kariwa, H. & Koster, F. T. ( 1997; ). Hantavirus pulmonary syndrome: CD8+ and CD4+ cytotoxic T lymphocytes to epitopes on Sin Nombre virus nucleocapsid protein isolated during acute illness. Virology 238, 380-390.[CrossRef]
    [Google Scholar]
  14. Geysen, H. M., Rodda, S. J., Mason, T. J., Tribbick, G. & Schoofs, P. G. ( 1987; ). Strategies for epitope analysis using peptide synthesis. Journal of Immunological Methods 102, 259-274.[CrossRef]
    [Google Scholar]
  15. Hjelle, B., Jenison, S. A., Goade, D. E., Green, W. B., Feddersen, R. M. & Scott, A. A. ( 1995; ). Hantaviruses: clinical, microbiologic, and epidemiologic aspects. Critical Reviews in Clinical Laboratory Sciences 32, 469-508.[CrossRef]
    [Google Scholar]
  16. Hörling, J., Lundkvist, Å., Jaarola, M., Plyusnin, A., Tegelström, H., Persson, K., Lehväslaiho, H., Hörnfeldt, B., Vaheri, A. & Niklasson, B. ( 1996; ). Distribution and genetic heterogeneity of Puumala virus in Sweden. Journal of General Virology 77, 2555-2562.[CrossRef]
    [Google Scholar]
  17. Huang, C., Jin, B., Wang, M., Li, E. & Sun, C. ( 1994; ). Hemorrhagic fever with renal syndrome: relationship between pathogenesis and cellular immunity. Journal of Infectious Diseases 169, 868-870.[CrossRef]
    [Google Scholar]
  18. Kanerva, M., Mustonen, J. & Vaheri, A. ( 1998; ). Pathogenesis of Puumala and other hantavirus infections. Reviews in Medical Virology 8, 67-86.[CrossRef]
    [Google Scholar]
  19. Krakauer, T., Leduc, J. W., Morrill, J. C., Anderson, A. O. & Krakauer, H. ( 1994; ). Serum levels of alpha and gamma interferons in hemorrhagic fever with renal syndrome. Viral Immunology 7, 97-101.[CrossRef]
    [Google Scholar]
  20. Lee, H. W., Lee, P. W. & Johnson, K. M. ( 1978; ). Isolation of the etiologic agent of Korean hemorrhagic fever. Journal of Infectious Diseases 137, 298-308.[CrossRef]
    [Google Scholar]
  21. Linderholm, M., Ahlm, C., Settergren, B., Waage, A. & Tärnvik, A. ( 1996; ). Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. Journal of Infectious Diseases 173, 38-43.[CrossRef]
    [Google Scholar]
  22. Lopez, N., Padula, P., Rossi, C., Lazaro, M. E. & Franze-Fernandez, M. T. ( 1996; ). Genetic identification of a new hantavirus causing severe pulmonary syndrome in Argentina. Virology 220, 223-226.[CrossRef]
    [Google Scholar]
  23. Lundkvist, Å. & Niklasson, B. ( 1992; ). Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins: identification of epitopes involved in neutralization. Archives of Virology 126, 93-105.[CrossRef]
    [Google Scholar]
  24. Lundkvist, Å. & Niklasson, B. ( 1994; ). Haemorrhagic fever with renal syndrome and other hantavirus infections. Reviews in Medical Virology 4, 177-184.[CrossRef]
    [Google Scholar]
  25. Lundkvist, Å., Fatouros, A. & Niklasson, B. ( 1991; ). Antigenic variation of European haemorrhagic fever with renal syndrome virus strains characterized using bank vole monoclonal antibodies. Journal of General Virology 72, 2097-2103.[CrossRef]
    [Google Scholar]
  26. Lundkvist, Å., Hörling, J. & Niklasson, B. ( 1993; ). The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays. Archives of Virology 130, 121-130.[CrossRef]
    [Google Scholar]
  27. Lundkvist, Å., Björsten, S., Niklasson, B. & Ahlborg, N. ( 1995; ). Mapping of B-cell determinants in the nucleocapsid protein of Puumala virus: definition of epitopes specific for acute immunoglobulin G recognition in humans. Clinical and Diagnostic Laboratory Immunology 2, 82-86.
    [Google Scholar]
  28. Lundkvist, Å., Kallio-Kokko, H., Sjölander, K. B., Lankinen, H., Niklasson, B., Vaheri, A. & Vapalahti, O. ( 1996; ). Characterization of Puumala virus nucleocapsid protein: identification of B-cell epitopes and domains involved in protective immunity. Virology 216, 397-406.[CrossRef]
    [Google Scholar]
  29. Lundkvist, Å., Hukic, M., Hörling, J., Gilljam, M., Nichol, S. & Niklasson, B. ( 1997a; ). Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera. Journal of Medical Virology 53, 51-59.[CrossRef]
    [Google Scholar]
  30. Lundkvist, Å., Cheng, Y., Sjölander, K. B., Niklasson, B., Vaheri, A. & Plyusnin, A. ( 1997b; ). Cell culture adaptation of Puumala hantavirus changes the infectivity for its natural reservoir, Clethrionomys glareolus, and leads to accumulation of mutants with altered genomic RNA S segment. Journal of Virology 71, 9515-9523.
    [Google Scholar]
  31. Mori, M., Rothman, A. L., Kurane, I., Montoya, J. M., Nolte, K. B., Norman, J. E., Waite, D. C., Koster, F. T. & Ennis, F. A. ( 1999; ). High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome. Journal of Infectious Diseases 179, 295-302.[CrossRef]
    [Google Scholar]
  32. Mustonen, J., Partanen, J., Kanerva, M., Pietila, K., Vapalahti, O., Pasternack, A. & Vaheri, A. ( 1998; ). Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus. Scandinavian Journal of Immunology 47, 277-279.[CrossRef]
    [Google Scholar]
  33. Nichol, S. T., Spiropoulou, C. F., Morzunov, S., Rollin, P. E., Ksiazek, T. G., Feldmann, H., Sanchez, A., Childs, J., Zaki, S. & Peters, C. J. ( 1993; ). Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 262, 914-917.[CrossRef]
    [Google Scholar]
  34. Pensiero, M. N., Sharefkin, J. B., Dieffenbach, C. W. & Hay, J. ( 1992; ). Hantaan virus infection of human endothelial cells. Journal of Virology 66, 5929-5936.
    [Google Scholar]
  35. Plyusnin, A., Vapalahti, O. & Vaheri, A. ( 1996; ). Hantaviruses: genome structure, expression and evolution. Journal of General Virology 77, 2677-2687.[CrossRef]
    [Google Scholar]
  36. Plyusnin, A., Krüger, D. H. & Lundkvist, Å. (2000). Hantavirus infections in Europe. Advances in Virus Research (in press).
  37. Sällberg, M., Rudén, U., Magnius, L. O., Norrby, E. & Wahren, B. ( 1991; ). Rapid ‘tea-bag’ peptide synthesis using 9-fluorenylmethoxycarbonyl (Fmoc) protected amino acids applied for antigenic mapping of viral proteins. Immunology Letters 30, 59-68.[CrossRef]
    [Google Scholar]
  38. Schmaljohn, C. S. ( 1996; ). Molecular biology of hantaviruses. In The Bunyaviridae , pp. 63-90. Edited by R. M. Elliott. New York:Plenum Press.
  39. Schmaljohn, C. S., Chu, Y. K., Schmaljohn, A. L. & Dalrymple, J. M. ( 1990; ). Antigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants. Journal of Virology 64, 3162-3170.
    [Google Scholar]
  40. Settergren, B., Ahlm, C., Juto, P. & Niklasson, B. ( 1991; ). Specific Puumala IgG virus half a century after haemorrhagic fever with renal syndrome. Lancet 338, 66.
    [Google Scholar]
  41. Stevens, T. L., Bossie, A., Sanders, V. M., Fernandez-Botran, R., Coffman, R. L., Mosmann, T. R. & Vitetta, E. S. ( 1988; ). Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 334, 255-258.[CrossRef]
    [Google Scholar]
  42. Temonen, M., Vapalahti, O., Holthofer, H., Brummer-Korvenkontio, M., Vaheri, A. & Lankinen, H. ( 1993; ). Susceptibility of human cells to Puumala virus infection. Journal of General Virology 74, 515-518.[CrossRef]
    [Google Scholar]
  43. Temonen, M., Mustonen, J., Helin, H., Pasternack, A., Vaheri, A. & Holthofer, H. ( 1996; ). Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study. Clinical Immunology and Immunopathology 78, 47-55.[CrossRef]
    [Google Scholar]
  44. Van Epps, H. L., Schmaljohn, C. S. & Ennis, F. A. ( 1999; ). Human memory cytotoxic T-lymphocyte (CTL) responses to Hantaan virus infection: identification of virus-specific and cross-reactive CD8+ CTL epitopes on nucleocapsid protein. Journal of Virology 73, 5301-5308.
    [Google Scholar]
  45. Vapalahti, O., Kallio-Kokko, H., Narvanen, A., Julkunen, I., Lundkvist, Å., Plyusnin, A., Lehvaslaiho, H., Brummer-Korvenkontio, M., Vaheri, A. & Lankinen, H. ( 1995; ). Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response. Journal of Medical Virology 46, 293-303.[CrossRef]
    [Google Scholar]
  46. Vapalahti, O., Lundkvist, Å., Kallio-Kokko, H., Paukku, K., Julkunen, I., Lankinen, H. & Vaheri, A. ( 1996; ). Antigenic properties and diagnostic potential of Puumala virus nucleocapsid protein expressed in insect cells. Journal of Clinical Microbiology 34, 119-125.
    [Google Scholar]
  47. Yoshimatsu, K., Yoo, Y. C., Yoshida, R., Ishihara, C., Azuma, I. & Arikawa, J. ( 1993; ). Protective immunity of Hantaan virus nucleocapsid and envelope protein studied using baculovirus-expressed proteins. Archives of Virology 130, 365-376.[CrossRef]
    [Google Scholar]
  48. Yoshimatsu, K., Arikawa, J., Tamura, M., Yoshida, R., Lundkvist, Å., Niklasson, B., Kariwa, H. & Azuma, I. ( 1996; ). Characterization of the nucleocapsid protein of Hantaan virus strain 76-118 using monoclonal antibodies. Journal of General Virology 77, 695-704.[CrossRef]
    [Google Scholar]
  49. Zaki, S. R., Greer, P. W., Coffield, L. M., Goldsmith, C. S., Nolte, K. B., Foucar, K., Feddersen, R. M., Zumwalt, R. E., Miller, G. L., Khan, A. S., Rollin, P. E., Ksiazek, T. G., Nichol, S. T., Mahy, B. W. J. & Peters, C. J. ( 1995; ). Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. American Journal of Pathology 146, 552-579.
    [Google Scholar]
  50. Zhang, X. K., Takashima, I. & Hashimoto, N. ( 1989; ). Characteristics of passive immunity against hantavirus infection in rats. Archives of Virology 105, 235-246.[CrossRef]
    [Google Scholar]
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