SELECTIVE TOLERANCE TO THE E1-PROTEIN OF RUBELLA-VIRUS IN CONGENITAL-RUBELLA SYNDROME

Rubella virus (RV) infection of the fetus in the first trimester of pr egnancy usually results in severe birth defects collectively termed Co ngenital Rubella Syndrome (CRS) and is frequently associated with prol onged RV persistence in the infant. Immunological tolerance to RV is b elieved to contribute to viral persistence, but the mechanism for this is unknown. In this study, RV-specific antibody responses in CRS pati ents and healthy controls who had experienced Rubella infection postna tally were compared to determine if there were differences that might account for RV persistence in the former group. Levels and functional affinities of IgG specific for individual RV proteins (E1, E2, and C) were measured by enzyme immunoassay (EIA). Relative amounts of RV prot ein-specific IgG directed to linear and topographic epitopes were comp ared by immunoblots run under reducing or nonreducing conditions, resp ectively, and biological activity was determined by hemagglutination i nhibition (HAI) assay. Results showed that both CRS patients and contr ol subjects had comparably high levels of IgG directed to whole RV and to RV E2 and C proteins as measured by EIA. However, in contrast to t he controls, CRS patients were found to have significantly reduced lev els of antibodies directed to RV E1 protein and its linear (but not to pographic) epitopes. Also, functional affinities of specific IgG direc ted to whole RV and E1 protein, as well as hemagglutination inhibition titers, were found to be significantly lower in CRS patients than in controls. The data suggest that intrauterine exposure to RV may result in selective immunological tolerance to the RV E1 protein. A model is presented that accommodates the serological findings,of this investig ation within a proposed mechanism of RV persistence resulting from sel ective immunological tolerance to RV E1 protein.