A
hantavirus infection is followed by a prominent antibody response to the viral
nucleocapsid protein.
Antibodies from patients infected with one hantavirus cross-react to varying degrees with the
nucleocapsid protein of other viruses of the genus. We studied the cross-reactivity in serially obtained blood samples from 17 patients with
nephropathia epidemica, a European form of
hemorrhagic fever with renal syndrome caused by Puumala virus. Recombinant truncated
nucleocapsid protein (aa 1-117) of Puumala virus and four other hantaviruses, Hantaan, Seoul, Dobrava and Sin Nombre viruses, were used as
antigens in an indirect ELISA. In most patients, an
IgG response to the Puumala virus derived
recombinant protein was detected within 2-8 days of onset of disease, remained high for 2-5 months, and declined gradually within 2-3 years. All patients had
IgG antibodies cross-reacting with the
nucleocapsid protein of Sin Nombre virus. The ratio of the ELISA values obtained with Sin Nombre vs. Puumala virus
protein as
antigen increased with time after onset of disease. To a lesser extent, cross-reacting
IgG antibodies also occurred to Hantaan, Seoul, and Dobrava virus
antigens. In the acute phase of the disease, two patients showed
IgG antibodies to one or more of these 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 conclusion, after onset of
nephropathia epidemica the
IgG response to the
Puumala virus nucleocapsid protein was associated with a gradually increasing cross-reactivity to the
nucleocapsid protein of heterologous hantavirus. Our findings have implications for the interpretation of serological data, both in the diagnostics of
nephropathia epidemica and in seroprevalence studies.