CHARACTERIZATION OF MENGO-VIRUS NEUTRALIZATION EPITOPES .2. INFECTIONOF MICE WITH AN ATTENUATED VIRUS

A panel of five neutralizing monoclonal antibodies was generated from mice immunized with an attenuated strain of Mengo virus. Four of the a ntibodies were used to select mutants of Mengo virus which were able t o escape neutralization by the selecting antibody, but it was not poss ible to select mutants which could escape neutralization by the fifth antibody. The capsid coding region of the RNA genome of each mutant wa s directly sequenced to identify the mutation(s) responsible for the n eutralization escape phenotype. These results are compared to those of a previous study in which immunogenic determinants recognized by neut ralizing antibodies generated against pentameric capsid subunits were located on the external surface of the Mengo virion. We have confirmed the existence of the previously identified immunogenic determinant in VP3 (site 2) as well as an immunodominant determinant in VP2 (site 1) . Two previously uncharacterized determinants, located in surface loop s of VP1 (sites 3 and 4), were also identified. None of the mutations conferring the neutralization escape phenotype was found near the surf ace depressions on the virion which are believed to be the receptor bi nding sites. (C) 1995 Academic Press, Inc.