Use of recombinant nucleocapsid proteins of the hantaan and nephropathia epidemica serotypes of Hantaviruses as immunodiagnostic antigens

Hantavirus nucleocapsid protein has previously been identified as the major antigen recognized by the humoral immune response in hemorrhagic fever with renal syndrome (HFRS). It was therefore considered to be a suitable antigen for the development of rapid and reliable immunodiagnostic assays. Genes encoding the nucleocapsid proteins of two Hantavirus strains, one of the Puumala serotype [nephropathia epidemica virus (NEV)] and the other of the Hantaan serotype were expressed in E. coli, and the expression products were used as diagnostic antigens in solid-phase enzyme immunoassays. The assays were used to detect IgG- and IgM-antibodies in sera of HFRS patients originating from different geographic regions (China, Germany, Greece, Yugoslavia, Scandinavia). ELISA was highly sensitive and proved to be superior to the indirect immunofluorescence assay. Both antigens were necessary to diagnose all HFRS cases originating from the different countries. Most of the sera revealed a predominant reactivity with either 1 of the 2 antigens, allowing the characterization of the etiologic virus as Hantaan-like or NEV-like. The results of the analysis of sera obtained from China and Greece suggested that the Hantaviruses prevalent in these countries are closely related to the Hantaan serotype. In contrast, an NEV-like reactivity was observed in Central and Northern European patients. In the sera of Yugoslav patients both reactivity patterns were found, suggesting that both virus types occur in the Balkan region.