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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-1-129
2001-01-01
2021-07-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/1/0820129a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-1-129&mimeType=html&fmt=ahah

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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
  18. Kanerva M., Mustonen J., Vaheri A. 1998; Pathogenesis of Puumala and other hantavirus infections. Reviews in Medical Virology 8:67–86
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
  24. Lundkvist Å., Niklasson B. 1994; Haemorrhagic fever with renal syndrome and other hantavirus infections. Reviews in Medical Virology 4:177–184
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
  36. Plyusnin A., Krüger D. H., Lundkvist Å. 2000; Hantavirus infections in Europe. Advances in Virus Research (in press)
    [Google Scholar]
  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
    [Google Scholar]
  38. Schmaljohn C. S. 1996; Molecular biology of hantaviruses. In The Bunyaviridae pp 63–90 Edited by Elliott R. M. New York: Plenum Press;
    [Google Scholar]
  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
    [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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-1-129
Loading
/content/journal/jgv/10.1099/0022-1317-82-1-129
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error