Topological mapping of antigenic sites on the Rift Valley fever virus envelope glycoproteins using monoclonal antibodies.

A panel of 17 monoclonal antibodies (MAbs) to the G1 and G2 envelope glycoproteins of Rift Valley fever (RVF) virus were used to analyze the topography and functional properties of the viral antigenic sites. Four heterogeneous antigenic regions which may be interlinked were identified on the G1 protein and four distinct domains on the G2 protein by competitive binding assays. Comparison of the biological activities and epitope specificities of the MAbs against G1 showed that the antigenic domains I, II, and IV were involved in virus neutralization and haemagglutination at different potencies. For both the G1 and G2 proteins, determinants mapping to domain G1 Ia and G2 Ia were associated with very strong neutralization independent of complement (C'), suggesting that they represent biologically important areas. Domain G2 II was involved in haemagglutination and weak C' dependent neutralization while the other two G2 regions had no haemagglutination function and neutralized to a low level only in the presence of C'. Epitopes Ia and IIb on G1 and Ia and IIa on G2 were also associated with protection of mice against virulent RVFV infection, indicating that both envelope glycoproteins play an important role in RVF viral infection and pathogenesis.