Serogrouping and seroepidemiology of North European hantaviruses using a novel broadly targeted synthetic nucleoprotein antigen array.

: Hantaviruses are globally distributed zoonotic pathogens. Great diversity and high antigenic cross-reactivity makes diagnosis by traditional methods cumbersome. : 'Megapeptides', 119-120-mers from the amino terminus of the nucleoprotein of 16 hantaviruses, representing the four major branches of the hantavirus phylogenetic tree, were utilized in a novel IgG-based hantavirus suspension multiplex immunoassay (HSMIA) for detection of past hantavirus infections in 155 North European human samples. We compared HSMIA with established EIAs and focus reduction neutralization test (FRNT). : The Puumala hantavirus (PUUV) component in the HSMIA gave concordant results with a PUUV IgG EIA in 142 sera from Northern Sweden (of which 31 were EIA positive, 7 borderline and 104 EIA negative, sensitivity 30/31 = 97%, specificity 104/ 104 = 100%, 134/135 = 99% concordance), with another immunoassay in 40 PUUV IgG positive sera from Finland (36/40 = 90% sensitivity), and was concordant in 8 of 11 cases with PUUV and DOBV neutralization titers, respectively. Two major IgG reactivity patterns were found: (i) a PUUV-specific pattern covering phylogroup IV and its serogroups B and C; and (ii) a Dobrava virus (DOBV)-specific pattern, covering the serogroup A portion of phylogroup III. In addition, we found several minor patterns with reactivity to only one or two megapeptides indicating additional hantaviruses infecting humans in the Swedish and Finnish populations. : The broadly reactive and rational HSMIA yielded results highly correlated with the established PUUV EIAs and the NT results. It is a sensitive and specific assay, which will be suited for efficient serosurveillance of hantaviruses in humans. Its use in animals should be further investigated.