Summary
Enzyme-linked immunosorbent assays for determination of antibodies directed to the nucleocapsid protein (N) or to either of the two envelope glycoproteins (G1 and G2) of Puumala virus were designed and evaluated. The assays were proven to be entirely restricted for each viral structural protein by biotin-labelled monoclonal antibodies. Sera from sequentially bled nephropathia epidemica patients (acute, convalescent, and 2-year sera) and sera from 10–20 year convalescents were examined for antibody specificity. All but one (n=19) acute phase sera were shown to contain IgM antibodies directed to all three viral proteins. In the convalescent specimens the proportions of IgM to the different viral components were similar, but lower, when compared to the acute samples. Low levels of IgM against N and G2 were found in two out of ten 2-year sera. No virus-specific IgM were detected in sera drawn 10–20 years after infection. IgG antibodies to all three viral proteins were detected in all except one acute phase serum. The IgG response initially increased more rapidly to N, as compared to the anti-glycoprotein responses. The levels of glycoprotein-specific IgG were considerably increased 2 years after the disease, when compared to the levels detected in the convalescent specimens. The levels and specificities of IgG in very late convalescent sera (drawn 10–20 years after disease) resembled those detected 2 years after infection.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Yanagihara R, Gajdusek DC (1988) Hemorrhagic fever with renal syndrome: a historical perspective and review of recent advances. In: Gear JHS (eds) CRC Handbook of viral and rickettsial hemorrhagic fevers. CRC Press, Boca Raton, pp 151–188
Schmaljohn CS, Hasty SE, Dalrymple JM, Leduc JW, Lee HW, Von Bonsdorff CH, Brummer-Korvenkontio M, Vaheri A, Tsai TF, Regnery HL, Goldgaber D, Lee PW (1985) Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science 227: 1041–1044
Elliott RM (1990) Molecular biology of the Bunyaviridae. J Gen Virol 71: 501–522
Lähdevirta J (1971) Nephropathia epidemica in Finland. A clinical, histological and epidemiological study. Ann Clin Res 3 [Suppl 8]
Brummer-Korvenkontio M, Vaheri A, Hovi T, von Bonsdorff C-H, Vuorimies J, Manni T, Penttinen K, Oker-Blom N, Lähdevirta J (1980) Nephropathia epidemica. Detection of antigen in bank voles and serological diagnosis of human infection. J Infect Dis 141: 131–134
Sheshberadaran H, Niklasson B, Tkachenko EA (1988) Antigenic relationship between hantaviruses analysed by immunoprecipitation. J Gen Virol 69: 2645–2651
Niklasson B, Jonsson M, Lundkvist Å, Hörling J, Tkachenko EA (1991) Comparison of European isolates of viruses causing hemorrhagic fever with renal syndrome by a neutralization test. Am J Trop Med Hyg 45: 660–665
Lee HW, Lee PW, Johnson KM (1978) Isolation of the etiologic agent of Korean hemorrhagic fever. J Infect Dis 137: 298–308
Lundkvist Å, Niklasson B (1992) Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins; identification of epitopes involved in neutralization. Arch Virol 126: 93–105
Brummer-Korventkontio M, Henttonen H, Vaheri A (1982) Hemorrhagic fever with renal syndrome in Finland: ecology and virology of nephropathia epidemica. Scan J Infect Dis [Suppl 36]: 88–91
Niklasson B, Tkachenko E, Ivanov AP, Van der Groen G, Wiger D, Andersen HK, LeDuc J, Kjellson T, Nyström K (1990) Haemorrhagic fever with renal syndrome: Evaluation of ELISA for detection of Puumala-virus-specific IgG and IgM. Res Virol 141: 637–648
Settergren B, Ahlm C, Juto B, Niklasson B (1991) Specific Puumala virus IgG half a century after haemorrhagic fever with renal syndrome. Lancet 338: 66
Hörling J, Lundkvist Å, Niklasson B (1992) Antibodies to Puumala virus in humans determined by neutralization test. J Virol Methods 39: 139–147
Niklasson B, Kjelsson T (1988) Detection of nephropathia epidemica (Puumala virus)-specific immnoglobulin M by enzyme-linked immunosorbent assay. J Clin Microbiol 26: 1519–1523
Lundkvist Å, Fatouros A, Niklasson B (1991) Antigenic variation of European haemorrhagic fever with renal syndrome virus strains characterized using bank vole monoclonal antibodies. J Gen Virol 72: 2097–2103
Harlow E, Lane D (1988) Antibodies: a laboratory manual, 1st edn. Cold Spring Harbor Laboratory, Cold Spring Harbor
Zöller L, Scholz J, Stohwasser R, Giebel LB, Sethi KK, Bautz EKF, Darai G (1989) Immunoblot analysis of the serological response in hantavirus infections. J Med Virol 27: 231–237
Bogdanova SB, Gavrilovskaya IN, Boyko VA, Prokhorova NA, Linev MB, Apekina NS, Gorbachkova YeA, Rymalov NIV, Bernshteyn AD, Chumakov MP (1987) Persistent infection caused by hemorrhagic fever with renal syndrome in red mice (Clethrionomys glareolus), natural hosts of the virus. Mikrobiol Zh 49: 99–106
Yamanishi K, Dantas HR, Takahashi Y, Yamanouchi T, Domae K, Takahashi Y, Tanishita O (1984) Antigenic differences between two viruses, isolated in Japan and Korea, that cause hemorrhagic fever with renal syndrome. J Virol 52: 231–237
Arikawa J, Schmaljohn AL, Dalrymple JM, Schmaljohn CS (1989) Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol 70: 615–624
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lundkvist, Å., Hörling, J. & Niklasson, B. The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays. Archives of Virology 130, 121–130 (1993). https://doi.org/10.1007/BF01319001
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01319001