The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays.

Enzyme-linked immunosorbent assays for determination of antibodies directed to the nucleocapsid protein (N) or to either of the two envelope glycoproteins (G1 and G2) of Puumala virus were designed and evaluated. The assays were proven to be entirely restricted for each viral structural protein by biotin-labelled monoclonal antibodies. Sera from sequentially bled nephropathia epidemica patients (acute, convalescent, and 2-year sera) and sera from 10-20 year convalescents were examined for antibody specificity. All but one (n = 19) acute phase sera were shown to contain IgM antibodies directed to all three viral proteins. In the convalescent specimens the proportions of IgM to the different viral components were similar, but lower, when compared to the acute samples. Low levels of IgM against N and G2 were found in two out of ten 2-year sera. No virus-specific IgM were detected in sera drawn 10-20 years after infection. IgG antibodies to all three viral proteins were detected in all except one acute phase serum. The IgG response initially increased more rapidly to N, as compared to the anti-glycoprotein responses. The levels of glycoprotein-specific IgG were considerably increased 2 years after the disease, when compared to the levels detected in the convalescent specimens. The levels and specificities of IgG in very late convalescent sera (drawn 10-20 years after disease) resembled those detected 2 years after infection.