Abstract
Nephropathia epidemica (NE), Puumala (PUU) virus infection, is a febrile disease which is commonly associated with acute renal impairment. To differentiate NE from other acute febrile illnesses, a rapid and reliable serological diagnosis is important, and a number of different protocols have recently been introduced. In the present report we describe a comparative evaluation of six PUU virus immunoglobulin M (IgM) and seven IgG enzyme-linked immunosorbent assay (ELISA) protocols based on native, Escherichia coli-expressed, or baculovirus-expressed nucleocapsid protein (N). Neutralization and immunofluorescence assays were included for comparison. Equally high sensitivities and specificities were obtained with three mu-capture-based IgM ELISAs using native, baculovirus-expressed, and E. coli-expressed N antigens, respectively, and by an ELISA based on purified E. coli-expressed full-length N adsorbed to solid phase. The assays based on truncated amino-terminal N proteins, including a commercially available PUU virus IgM ELISA, all showed lower sensitivities. For detection of PUU virus-specific IgG, ELISAs based on monoclonal antibody-captured native or baculovirus-expressed N antigens showed optimal sensitivities and specificities, while the assays based on E. coli-expressed N did not detect all PUU virus IgG-positive serum samples. A commercially available PUU virus IgG ELISA based on E. coli-expressed amino-terminal N showed a significantly lower sensitivity than those of all other IgG assays.
Full Text
The Full Text of this article is available as a PDF (145.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brummer-Korvenkontio M., Vaheri A., Hovi T., von Bonsdorff C. H., Vuorimies J., Manni T., Penttinen K., Oker-Blom N., Lähdevirta J. Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection. J Infect Dis. 1980 Feb;141(2):131–134. doi: 10.1093/infdis/141.2.131. [DOI] [PubMed] [Google Scholar]
- Chen H. X., Qiu F. X., Dong B. J., Ji S. Z., Li Y. T., Wang Y., Wang H. M., Zuo G. F., Tao X. X., Gao S. Y. Epidemiological studies on hemorrhagic fever with renal syndrome in China. J Infect Dis. 1986 Sep;154(3):394–398. doi: 10.1093/infdis/154.3.394. [DOI] [PubMed] [Google Scholar]
- Elgh F., Linderholm M., Wadell G., Juto P. 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. 1996 Jun;6(1):17–26. doi: 10.1016/0928-0197(96)00208-5. [DOI] [PubMed] [Google Scholar]
- Elgh F., Lundkvist A., Alexeyev O. A., Stenlund H., Avsic-Zupanc T., Hjelle B., Lee H. W., Smith K. J., Vainionpä R., Wiger D. 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. 1997 May;35(5):1122–1130. doi: 10.1128/jcm.35.5.1122-1130.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elgh F., Lundkvist A., Alexeyev O. A., Wadell G., Juto P. A major antigenic domain for the human humoral response to Puumala virus nucleocapsid protein is located at the amino-terminus. J Virol Methods. 1996 May;59(1-2):161–172. doi: 10.1016/0166-0934(96)02042-3. [DOI] [PubMed] [Google Scholar]
- Elgh F., Wadell G., Juto P. Comparison of the kinetics of Puumala virus specific IgM and IgG antibody responses in nephropathia epidemica as measured by a recombinant antigen-based enzyme-linked immunosorbent assay and an immunofluorescence test. J Med Virol. 1995 Feb;45(2):146–150. doi: 10.1002/jmv.1890450206. [DOI] [PubMed] [Google Scholar]
- Elliott R. M. Molecular biology of the Bunyaviridae. J Gen Virol. 1990 Mar;71(Pt 3):501–522. doi: 10.1099/0022-1317-71-3-501. [DOI] [PubMed] [Google Scholar]
- Hedman K., Vaheri A., Brummer-Korvenkontio M. Rapid diagnosis of hantavirus disease with an IgG-avidity assay. Lancet. 1991 Nov 30;338(8779):1353–1356. doi: 10.1016/0140-6736(91)92235-t. [DOI] [PubMed] [Google Scholar]
- Hörling J., Lundkvist A., Huggins J. W., Niklasson B. Antibodies to Puumala virus in humans determined by neutralization test. J Virol Methods. 1992 Sep;39(1-2):139–147. doi: 10.1016/0166-0934(92)90132-w. [DOI] [PubMed] [Google Scholar]
- Hörling J., Lundkvist A., Persson K., Mullaart M., Dzagurova T., Dekonenko A., Tkachenko E., Niklasson B. Detection and subsequent sequencing of Puumala virus from human specimens by PCR. J Clin Microbiol. 1995 Feb;33(2):277–282. doi: 10.1128/jcm.33.2.277-282.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ivanov A., Vapalahti O., Lankinen H., Tkachenko E., Vaheri A., Niklasson B., Lundkvist A. Biotin-labeled antigen: a novel approach for detection of Puumala virus-specific IgM. J Virol Methods. 1996 Oct;62(1):87–92. doi: 10.1016/0166-0934(96)02090-3. [DOI] [PubMed] [Google Scholar]
- Jenison S., Yamada T., Morris C., Anderson B., Torrez-Martinez N., Keller N., Hjelle B. Characterization of human antibody responses to four corners hantavirus infections among patients with hantavirus pulmonary syndrome. J Virol. 1994 May;68(5):3000–3006. doi: 10.1128/jvi.68.5.3000-3006.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kallio-Kokko H., Vapalahti O., Hedman K., Brummer-Korvenkontio M., Vaheri A. Puumala virus antibody and immunoglobulin G avidity assays based on a recombinant nucleocapsid antigen. J Clin Microbiol. 1993 Mar;31(3):677–680. doi: 10.1128/jcm.31.3.677-680.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim G. R., Lee Y. T., Park C. H. A new natural reservoir of hantavirus: isolation of hantaviruses from lung tissues of bats. Arch Virol. 1994;134(1-2):85–95. doi: 10.1007/BF01379109. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Björsten S., Niklasson B., Ahlborg N. Mapping of B-cell determinants in the nucleocapsid protein of Puumala virus: definition of epitopes specific for acute immunoglobulin G recognition in humans. Clin Diagn Lab Immunol. 1995 Jan;2(1):82–86. doi: 10.1128/cdli.2.1.82-86.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lundkvist A., Björsten S., Niklasson B. Immunoglobulin G subclass responses against the structural components of Puumala virus. J Clin Microbiol. 1993 Feb;31(2):368–372. doi: 10.1128/jcm.31.2.368-372.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lundkvist A., Fatouros A., Niklasson B. Antigenic variation of European haemorrhagic fever with renal syndrome virus strains characterized using bank vole monoclonal antibodies. J Gen Virol. 1991 Sep;72(Pt 9):2097–2103. doi: 10.1099/0022-1317-72-9-2097. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Hukic M., Hörling J., Gilljam M., Nichol S., Niklasson B. Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera. J Med Virol. 1997 Sep;53(1):51–59. [PubMed] [Google Scholar]
- Lundkvist A., Hörling J., Niklasson B. The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays. Arch Virol. 1993;130(1-2):121–130. doi: 10.1007/BF01319001. [DOI] [PubMed] [Google Scholar]
- Niklasson B., Jonsson M., Lundkvist A., Horling J., Tkachenko E. Comparison of European isolates of viruses causing hemorrhagic fever with renal syndrome by a neutralization test. Am J Trop Med Hyg. 1991 Dec;45(6):660–665. doi: 10.4269/ajtmh.1991.45.660. [DOI] [PubMed] [Google Scholar]
- Niklasson B., Kjelsson T. Detection of nephropathia epidemica (Puumala virus)-specific immunoglobulin M by enzyme-linked immunosorbent assay. J Clin Microbiol. 1988 Aug;26(8):1519–1523. doi: 10.1128/jcm.26.8.1519-1523.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niklasson B., LeDuc J. W. Epidemiology of nephropathia epidemica in Sweden. J Infect Dis. 1987 Feb;155(2):269–276. doi: 10.1093/infdis/155.2.269. [DOI] [PubMed] [Google Scholar]
- Plyusnin A., Hörling J., Kanerva M., Mustonen J., Cheng Y., Partanen J., Vapalahti O., Kukkonen S. K., Niemimaa J., Henttonen H. 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. 1997 May;35(5):1090–1096. doi: 10.1128/jcm.35.5.1090-1096.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plyusnin A., Vapalahti O., Vaheri A. Hantaviruses: genome structure, expression and evolution. J Gen Virol. 1996 Nov;77(Pt 11):2677–2687. doi: 10.1099/0022-1317-77-11-2677. [DOI] [PubMed] [Google Scholar]
- Schmaljohn C. S., Hasty S. E., Dalrymple J. M., LeDuc J. W., Lee H. W., von Bonsdorff C. H., Brummer-Korvenkontio M., Vaheri A., Tsai T. F., Regnery H. L. Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science. 1985 Mar 1;227(4690):1041–1044. doi: 10.1126/science.2858126. [DOI] [PubMed] [Google Scholar]
- Sheshberadaran H., Niklasson B., Tkachenko E. A. Antigenic relationship between hantaviruses analysed by immunoprecipitation. J Gen Virol. 1988 Oct;69(Pt 10):2645–2651. doi: 10.1099/0022-1317-69-10-2645. [DOI] [PubMed] [Google Scholar]
- Tkachenko E. A., Donets M. A., Rezapkin G. V., Dzagurova T. K., Ivanov A. P., Leshchinskaya E. V., Reshetnikov I., Drozdov S. G., Slonova R. A., Somov G. P. Serotypes of HFRS (haemorrhagic fever with renal syndrome) virus in East European and Far Eastern U.S.S.R. Lancet. 1982 Apr 10;1(8276):863–863. doi: 10.1016/s0140-6736(82)91922-5. [DOI] [PubMed] [Google Scholar]
- Tsai T. F. Hemorrhagic fever with renal syndrome: mode of transmission to humans. Lab Anim Sci. 1987 Aug;37(4):428–430. [PubMed] [Google Scholar]
- Vapalahti O., Kallio-Kokko H., Närvänen A., Julkunen I., Lundkvist A., Plyusnin A., Lehväslaiho H., Brummer-Korvenkontio M., Vaheri A., Lankinen H. Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response. J Med Virol. 1995 Aug;46(4):293–303. doi: 10.1002/jmv.1890460402. [DOI] [PubMed] [Google Scholar]
- Vapalahti O., Kallio-Kokko H., Salonen E. M., Brummer-Korvenkontio M., Vaheri A. Cloning and sequencing of Puumala virus Sotkamo strain S and M RNA segments: evidence for strain variation in hantaviruses and expression of the nucleocapsid protein. J Gen Virol. 1992 Apr;73(Pt 4):829–838. doi: 10.1099/0022-1317-73-4-829. [DOI] [PubMed] [Google Scholar]
- Vapalahti O., Lundkvist A., Kallio-Kokko H., Paukku K., Julkunen I., Lankinen H., Vaheri A. Antigenic properties and diagnostic potential of puumala virus nucleocapsid protein expressed in insect cells. J Clin Microbiol. 1996 Jan;34(1):119–125. doi: 10.1128/jcm.34.1.119-125.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zöller L. G., Yang S., Gött P., Bautz E. K., Darai G. A novel mu-capture enzyme-linked immunosorbent assay based on recombinant proteins for sensitive and specific diagnosis of hemorrhagic fever with renal syndrome. J Clin Microbiol. 1993 May;31(5):1194–1199. doi: 10.1128/jcm.31.5.1194-1199.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zöller L., Faulde M., Meisel H., Ruh B., Kimmig P., Schelling U., Zeier M., Kulzer P., Becker C., Roggendorf M. Seroprevalence of hantavirus antibodies in Germany as determined by a new recombinant enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 1995 Apr;14(4):305–313. doi: 10.1007/BF02116523. [DOI] [PubMed] [Google Scholar]
- Zöller L., Yang S., Gött P., Bautz E. K., Darai G. Use of recombinant nucleocapsid proteins of the Hantaan and nephropathia epidemica serotypes of Hantaviruses as immunodiagnostic antigens. J Med Virol. 1993 Mar;39(3):200–207. doi: 10.1002/jmv.1890390305. [DOI] [PubMed] [Google Scholar]
- Zöller L., Yang S., Zeyer M. Rapid diagnosis of haemorrhagic fever with renal syndrome due to hantavirus. Lancet. 1991 Jul 20;338(8760):183–183. doi: 10.1016/0140-6736(91)90169-p. [DOI] [PubMed] [Google Scholar]