IDENTIFICATION OF MUTATIONS IN THE ROTAVIRUS PROTEIN VP4 THAT ALTER SIALIC-ACID-DEPENDENT INFECTION

To explore further the role of VP4 as the rotavirus cell attachment pr otein, VP7 monoreassortants derived from the sialic-acid-dependent sim ian strain RRV and from the sialic-acid-independent human strains D, D S-1 and ST-3 were tested for susceptibility of infectivity of neuramin idase-treated MA-104 cells, Infectivity of RRV x D VP7 and RRV x ST-3 VP7 monoreassortants decreased when sialic acid was removed from the c ell surface, However, of three separate RRV x DS-1 VP7 monoreassortant s tested, only one was sialic-acid-dependent, Sequence analysis showed that both sialic-acid-independent strains contained a single amino ac id change, Lys to Arg, at position 187, In addition, sialic-acid-indep endent infectivity was seen in one of 14 RRV VP4 neutralization escape mutants tested, and this strain was found to have a Gly to Glu change at amino acid position 150. These results indicate that positions 150 and 187 of VP4 play an important role in early rotavirus-cell interac tions.