Skip to main content
Springer Nature Link
Log in

Specific humoral reaction of hemorrhagic fever with renal syndrome (HFRS) patients in China to recombinant nucleocapsid proteins from European hantaviruses

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. This study was initiated to investigate the reactivity of antibodies in sera of Chinese HFRS patients with the recombinant nucleocapsid proteins (rNPs) of Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Puumala virus (PUUV), which are the prevalent hantavirus strains in Europe. Forty-eight pairs of acute and convalescent sera were collected from HFRS patients in Hubei, China (1985-2002) and tested by indirect IgG, IgA, and IgM enzyme-linked immunosorbent assays with six rNPs of European hantaviruses as coated antigens, respectively. The results showed that the sensitivity of rNPs against IgG was HTNV-rNP > DOBV-rNP > PUUV-rNP, while the sensitivity against IgA was DOBV-rNP > HTNV-rNP > PUUV-rNP. Quantitative analysis revealed both acute and convalescent sera from HFRS patients predominantly exhibit high levels of IgA. Although PUUV-rNPs showed very weak reactivity to the three kinds of immunoglobulins in all samples, three pairs of sera unexpectedly cross-reacted strongly to all three PUUV-rNP subtypes. We first observe that HFRS patients’ sera from Hubei Province show new prevalent characteristics of cross-reacting with PUUV-rNPs and continued high level of IgA in convalescent phase, as well as in China.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Niklasson BS (1992) Haemorrhagic fever with renal syndrome, virological and epidemiological aspects. Pediatr Nephrol 6(2):201–204

    Article  PubMed  CAS  Google Scholar 

  2. Zeier M, Handermann M, Bahr U, Rensch B, Muller S, Kehm R, Muranyi W, Darai G (2005) New ecological aspects of hantavirus infection: a change of a paradigm and a challenge of prevention—a review. Virus Genes 30(2):157–180

    Article  PubMed  CAS  Google Scholar 

  3. Kariwa H, Yoshimatsu K, Arikawa J (2007) Hantavirus infection in East Asia. Comp Immunol Microbiol Infect Dis 30(5–6):341–356

    Article  PubMed  Google Scholar 

  4. Kruger DH, Ulrich R, Lundkvist AA (2001) Hantavirus infections and their prevention. Microbes Infect 3(13):1129–1144

    Article  PubMed  CAS  Google Scholar 

  5. Maes P, Clement J, Gavrilovskaya I, Van Ranst M (2004) Hantaviruses: immunology, treatment, and prevention. Viral Immunol 17(4):481–497

    Article  PubMed  CAS  Google Scholar 

  6. Plyusnin A, Kruger DH, Lundkvist A (2001) Hantavirus infections in Europe. Adv Virus Res 57:105–136

    Article  PubMed  CAS  Google Scholar 

  7. Childs JE, Kaufmann AF, Peters CJ, Ehrenberg RL (1993) Hantavirus infection—southwestern United States: interim recommendations for risk reduction. Centers for Disease Control and Prevention. MMWR Recomm Rep 42(RR-11):1–13

    PubMed  CAS  Google Scholar 

  8. Lee HW, van der Groen G (1989) Hemorrhagic fever with renal syndrome. Prog Med Virol 36:62–102

    PubMed  CAS  Google Scholar 

  9. Schmaljohn C, Hjelle B (1997) Hantaviruses: a global disease problem. Emerg Infect Dis 3(2):95–104

    Article  PubMed  CAS  Google Scholar 

  10. Vapalahti O, Mustonen J, Lundkvist A, Henttonen H, Plyusnin A, Vaheri A (2003) Hantavirus infections in Europe. Lancet Infect Dis 3(10):653–661

    Article  PubMed  Google Scholar 

  11. Nemirov K, Vapalahti O, Lundkvist A, Vasilenko V, Golovljova I, Plyusnina A, Niemimaa J, Laakkonen J, Henttonen H, Vaheri A, Plyusnin A (1999) Isolation and characterization of Dobrava hantavirus carried by the striped field mouse (Apodemus agrarius) in Estonia. J Gen Virol 80(Pt 2):371–379

    PubMed  CAS  Google Scholar 

  12. Sibold C, Ulrich R, Labuda M, Lundkvist A, Martens H, Schutt M, Gerke P, Leitmeyer K, Meisel H, Kruger DH (2001) Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species. J Med Virol 63(2):158–167

    Article  PubMed  CAS  Google Scholar 

  13. Song G (1999) Epidemiological progresses of hemorrhagic fever with renal syndrome in China. Chin Med J (Engl) 112((5):472–477

    CAS  Google Scholar 

  14. Tang LY, Yu T, Liu WX, Chen HX (2000) Study on types of hemorragic fever with renal syndrome in Chinese epidemic areas. Disease Surveillance 15(7):248–250

    Google Scholar 

  15. Chen HX, Luo CW, Chen F, Wang XH, Yang JH, Ma LJ, Hu JY, Sun HY, Yao ZH, Qiu JC (1999) Study and surveillance of HFRS (hemorrhage fever with renal syndrome) in China. Chinese Journal of Public Health 15(7):616–623

    Google Scholar 

  16. Wang H, Yoshimatsu K, Ebihara H, Ogino M, Araki K, Kariwa H, Wang Z, Luo Z, Li D, Hang C, Arikawa J (2000) Genetic diversity of hantaviruses isolated in china and characterization of novel hantaviruses isolated from Niviventer confucianus and Rattus rattus. Virology 278(2):332–345

    Article  PubMed  CAS  Google Scholar 

  17. Liu G, Li C, Hu GW, Li Y, Yao LS, Chen YQ, Huang B, Ren M, Chen YZ, Guan SX, Yu CY, Na BZ, Zhong XD, Sun YX, Li WX, Li DX (2003) Identification of Puumala like viruses in China. Zhonghua shi yan he lin chuang bing du xue za zhi 17(1):55–57

    PubMed  Google Scholar 

  18. Zhang YZ, Zou Y, Yan YZ, Hu GW, Yao LS, Du ZS, Jin LZ, Liu YY, Li MH, Chen HX, Fu ZF (2007) Detection of phylogenetically distinct Puumala-like viruses from red-grey vole Clethrionomys rufocanus in China. J Med Virol 79(8):1208–1218

    Article  PubMed  CAS  Google Scholar 

  19. Zou Y, Xiao QY, Dong X, Lv W, Zhang SP, Li MH, Plyusnin A, Zhang YZ (2008) Genetic analysis of hantaviruses carried by reed voles Microtus fortis in China. Virus Res 137(1):122–128

    Article  PubMed  CAS  Google Scholar 

  20. Zou Y, Wang JB, Gaowa HS, Yao LS, Hu GW, Li MH, Chen HX, Plyusnin A, Shao R, Zhang YZ (2008) Isolation and genetic characterization of hantaviruses carried by Microtus voles in China. J Med Virol 80(4):680–688

    Article  PubMed  CAS  Google Scholar 

  21. Cohen MS, Casals J, Hsiung GD, Kwei HE, Chin CC, Ge HC, Hsiang CM, Lee PW, Gibbs CJ Jr, Gajdusek DC (1981) Epidemic hemorrhagic fever in Hubei Province, The People's Republic of China: a clinical and serological study. Yale J Biol Med 54(1):41–55

    PubMed  CAS  Google Scholar 

  22. Xiao SY, Liang M, Schmaljohn CS (1993) Molecular and antigenic characterization of HV114, a hantavirus isolated from a patient with haemorrhagic fever with renal syndrome in China. J Gen Virol 74(Pt 8):1657–1659

    Article  PubMed  CAS  Google Scholar 

  23. Fang Y, Huang XH, Zhou Q, Hu EP, Guan HX (1995) The trend of epidemic situation changes of hemorrhagic fever with renal syndrome (HFRS) in early 1990s in Hubei Province. Chinese Journal of Vector Biology and Control 6(2):111–113

    Google Scholar 

  24. Yang ZQ, Zhang TM, Zhang MY, Zheng ZM, Hu ZJ, Qu CF, Zhu BL, Xiang JM, Huggins JW, Cosgriff TM, Smith JI (1989) A study on early viremia in patients with epidemic hemorrhagic fever (EHF) and the blockade therapy. National Medical Journal of China 69(11):621–624

    PubMed  CAS  Google Scholar 

  25. Elgh F, Lundkvist A, Alexeyev OA, Stenlund H, Avsic-Zupanc T, Hjelle B, Lee HW, Smith KJ, Vainionpaa R, Wiger D, Wadell G, Juto P (1997) Serological diagnosis of hantavirus infections by an enzyme-linked immunosorbent assay based on detection of immunoglobulin G and M responses to recombinant nucleocapsid proteins of five viral serotypes. J Clin Microbiol 35(5):1122–1130

    PubMed  CAS  Google Scholar 

  26. Petraityte R, Yang H, Hunjan R, Razanskiene A, Dhanilall P, Ulrich RG, Sasnauskas K, Jin L (2008) Development and evaluation of serological assays for detection of Hantaanvirus-specific antibodies in human sera using yeast-expressed nucleocapsid protein. J Virol Methods 148(1–2):89–95

    Article  PubMed  CAS  Google Scholar 

  27. Meisel H, Wolbert A, Razanskiene A, Marg A, Kazaks A, Sasnauskas K, Pauli G, Ulrich R, Kruger DH (2006) Development of novel immunoglobulin G (IgG), IgA, and IgM enzyme immunoassays based on recombinant Puumala and Dobrava hantavirus nucleocapsid proteins. Clin Vaccine Immunol 13(12):1349–1357

    Article  PubMed  CAS  Google Scholar 

  28. Razanskiene A, Schmidt J, Geldmacher A, Ritzi A, Niedrig M, Lundkvist A, Kruger DH, Meisel H, Sasnauskas K, Ulrich R (2004) High yields of stable and highly pure nucleocapsid proteins of different hantaviruses can be generated in the yeast Saccharomyces cerevisiae. J Biotechnol 111(3):319–333

    Article  PubMed  CAS  Google Scholar 

  29. Elgh F, Linderholm M, Wadell G, Juto P (1996) The clinical usefulness of a Puumalavirus recombinant nucleocapsid protein based enzyme-linked immunosorbent assay in the diagnosis of nephropathia epidemica as compared with an immunofluorescence assay. Clin Diagn Virol 6(1):17–26

    Article  PubMed  CAS  Google Scholar 

  30. Groen J, Gerding M, Jordans JG, Clement JP, Osterhaus AD (1994) Class and subclass distribution of hantavirus-specific serum antibodies at different times after the onset of nephropathia epidemica. J Med Virol 43(1):39–43

    Article  PubMed  CAS  Google Scholar 

  31. Meng XS, Chen YP, Li C, Yu JS, Guo YM, Zhang QF, Sun YL, Li DX (2003) Using recombinant antigens of Hantavirus to study the kinetics of serum IgA, IgG, IgM antibodies in the acute-phase of hemorrhagic fever renal syndrome. Zhonghua shi yan he lin chuang bing du xue za zhi 17(3):254–257

    PubMed  CAS  Google Scholar 

  32. de Carvalho NC, Bjorling E, Lundkvist A (2000) Immunoglobulin A responses to Puumala hantavirus. J Gen Virol 81(Pt 6):1453–1461

    Google Scholar 

  33. Elgh F, Linderholm M, Wadell G, Tarnvik A, Juto P (1998) Development of humoral cross-reactivity to the nucleocapsid protein of heterologous hantaviruses in nephropathia epidemica. FEMS Immunol Med Microbiol 22(4):309–315

    Article  PubMed  CAS  Google Scholar 

  34. Kato H, Kato R, Fujihashi K, McGhee JR (2001) Role of mucosal antibodies in viral infections. Curr Top Microbiol Immunol 260:201–228

    PubMed  CAS  Google Scholar 

  35. Dzagurova T, Tkachenko E, Slonova R, Ivanov L, Ivanidze E, Markeshin S, Dekonenko A, Niklasson B, Lundkvist A (1995) Antigenic relationships of hantavirus strains analysed by monoclonal antibodies. Arch Virol 140(10):1763–1773

    Article  PubMed  CAS  Google Scholar 

  36. Geldmacher A, Schmaler M, Kruger DH, Ulrich R (2004) Yeast-expressed hantavirus Dobrava nucleocapsid protein induces a strong, long-lasting, and highly cross-reactive immune response in mice. Viral Immunol 17(1):115–122

    Article  PubMed  CAS  Google Scholar 

  37. Li Q, Yang ZQ, Qu H, Xiao H (2005) Variability of G1 gene of hantaviruses occurring in the Hubei Province, P.R. China from 1985 to 2000. Acta Virol 49(1):51–57

    Article  PubMed  CAS  Google Scholar 

  38. Zhang Y, Zhang H, Dong X, Yuan J, Zhang H, Yang X, Zhou P, Ge X, Li Y, Wang LF, Shi Z (2010) Hantavirus outbreak associated with laboratory rats in Yunnan, China. Infect Genet Evol 10(5):638–644

    Article  PubMed  CAS  Google Scholar 

  39. Zou Y, Hu J, Wang ZX, Wang DM, Yu C, Zhou JZ, Fu ZF, Zhang YZ (2008) Genetic characterization of hantaviruses isolated from Guizhou, China: evidence for spillover and reassortment in nature. J Med Virol 80(6):1033–1041

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the physicians who assisted in the sample collection and Dr. K. Sasnauskas, Institute of Biotechnology, Vilnius, Lithuania for providing S. cerevisiae strains expressing N proteins. We would like to thank Dr. Rhea-Beth Markowitz, Medical College of Georgia, Augusta, Georgia, USA and Dr. Ying Lin, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China for editing assistance. This work was supported by the National High Technology Research and Development 863 Program of China (No. 2007AA02Z465), a grant from the National Natural Science Foundation of China (NSFC project No. 30770096) and the Open Grant of State Key Laboratory of Virology (2007-05).

Author information

Authors and Affiliations

  1. State Key Laboratory of Virology/ Institute of Medical Virology, School of Medicine, Wuhan University, 185 Donghu Road, Wuhan, 430071, P.R. China

    H.-R. Xiong, W. Chen, D.-Y. Liu, J.-X. Ling, J. Liu, Y.-J. Liu & Z.-Q. Yang

  2. Department of Basic Medicine, Xiamen University Medical College, Xiamen, 361005, P.R. China

    Q. Li

  3. Institute of Military Medical Sciences, Nanjing Command, Nanjing, 210002, P.R. China

    Y. Zhang

Authors
  1. H.-R. Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Q. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D.-Y. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J.-X. Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y.-J. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Z.-Q. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z.-Q. Yang.

Additional information

Hai-Rong Xiong and Qing Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiong, HR., Li, Q., Chen, W. et al. Specific humoral reaction of hemorrhagic fever with renal syndrome (HFRS) patients in China to recombinant nucleocapsid proteins from European hantaviruses. Eur J Clin Microbiol Infect Dis 30, 645–651 (2011). https://doi.org/10.1007/s10096-010-1134-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-010-1134-5

Keywords

Search

Navigation