{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:40:20Z","timestamp":1790052020308,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T00:00:00Z","timestamp":1133913600000},"content-version":"vor","delay-in-days":3781,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[1995,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Puumala virus (PUU) is a member of the <jats:italic>Hantavi rus<\/jats:italic> genus in the family <jats:italic>Bunyaviridae<\/jats:italic> and the etiologic agent of nephropathia epidemica (NE), a form of haemorrhagic fever with renal syndrome (HFRS). In this study we compared the immunofluorescence patterns of NE sera and antibodies raised against recombinant PUU proteins and confirm that the nucleocapsid protein is the major target in the early IgG response of NE patients and provides the molecular basis for simple and rapid differentiation between acute illness and old immunity by granular vs. diffuse fluorescence staining in the indirect immunofluorescence test. The differential kinetics of B\u2010cell responses to PUU nucleocapsid vs. envelope proteins was emphasized further by the end\u2010point titres of IgG antibodies to N, G1 and G2 proteins in NE patients. The granular fluorescence correlated with low IgG avidity in 99.8%. and diffuse fluorescence with high avidity in 100% of 617 NE sera studied. Epitope scanning with overlapping 14\u2010mer peptides covering the whole nucleocapsid protein by a shift of 3 amino acids revealed six major antigenic epitopes recognized by sera from acute\u2010phase NE patients. The epitopes clustered mainly in the hydrophilic regions, and two of them in a highly variable region which could probably serve as an antigen to distinguish serologically between infections of closely related hantaviruses, some apparently apathogenic, some causing lethal infections. The anti\u2010peptide epitope pattern varied between different individuals and a collection of several pinbound peptides was needed to be recognised by most NE sera studied. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.1890460402","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T02:42:06Z","timestamp":1172889726000},"page":"293-303","source":"Crossref","is-referenced-by-count":149,"title":["Human B\u2010cell epitopes of puumala virus nucleocapsid protein, the major antigen in early serological response"],"prefix":"10.1002","volume":"46","author":[{"given":"Olli","family":"Vapalahti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannimari","family":"Kallio\u2010Kokko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ale","family":"N\u00e4rv\u00e4nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Julkunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5ke","family":"Lundkvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Plyusnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Lehvaslaiho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Brummer\u2010Korvenkontio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Vaheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilkka","family":"Lankinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(92)90029-9"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-70-3-615"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90236-K"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890380211"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/141.2.131"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/153.5.997-a"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1022"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90841-9"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-71-3-501"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.1.178"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.1.113"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(91)90090-I"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890370409"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92235-T"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235607"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1128\/jvi.68.5.3000-3006.1994","article-title":"Characterisation of human antibody responses to Four Corners hantavirus infections among patients with hantavirus pulmonary syndrome","volume":"68","author":"Jenison S","year":"1994","journal-title":"Journal of Virology"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1128\/jcm.31.3.677-680.1993","article-title":"Puumala virus antibody and immunoglobulin G avidity assays based on recombinant nucleocapsid antigen","volume":"31","author":"Kallio\u2010Kokko H","year":"1993","journal-title":"Journal of Clinical Microbiology"},{"key":"e_1_2_1_19_1","volume-title":"Current Topics in Microbiology and Immunology, Bunyaviridae","author":"Kolakofsky D","year":"1993"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91865-J"},{"key":"e_1_2_1_21_1","first-page":"371","article-title":"Korean hemorrhagic fever. 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