Development of humoral cross-reactivity to the nucleocapsid protein of heterologous hantaviruses in nephropathia epidemica

A hantavirus infection is followed by a prominent antibody response to the viral nucleocapsid protein. Antibodies from patients infected with one hant avirus cross-react to varying degrees with the nucleocapsid protein of othe r viruses of the genus. We studied the cross-reactivity in serially obtaine d blood samples from 17 patients with nephropathia epidemica, a European fo rm of hemorrhagic fever with renal syndrome caused by Puumala virus. Recomb inant truncated nucleocapsid protein (aa 1-117) of Puumala virus and four o ther hantaviruses, Hantaan, Seoul, Dobrava and Sin Nombre viruses, were use d as antigens in an indirect ELISA. In most patients, an IgG response to th e Puumala virus derived recombinant protein was detected within 2-8 days of onset of disease, remained high for 2-5 months, and declined gradually wit hin 2-3 years. All patients had IgG antibodies cross-reacting with the nucl eocapsid protein of Sin Nombre virus. The ratio of the ELISA values obtaine d with Sin Nombre vs. Puumala virus protein as antigen increased with time after onset of disease. To a lesser extent, cross-reacting IgG antibodies a lso occurred to Hantaan, Seoul, and Dobrava virus antigens. In the acute ph ase of the disease, two patients showed IgG antibodies to one or more of th ese viruses whereas 2-5 months later, 11 of 16 patients had IgG antibodies to all three viruses. IgM and IgA responses to the nucleocapsid protein of Puumala virus were transitory and cross-reactivities were weak. In conclusi on, after onset of nephropathia epidemica the IgG response to the Puumala v irus nucleocapsid protein was associated with a gradually increasing cross- reactivity to the nucleocapsid protein of heterologous hantavirus. Our find ings have implications for the interpretation of serological data, both in the diagnostics of nephropathia epidemica and in seroprevalence studies. (C ) 1998 Published by Elsevier Science B.V. All rights reserved.