Subgroup specific protection of mice from respiratory syncytial virus infection with peptides encompassing the amino acid region 174–187 from the G glycoprotein: the role of cysteinyl residues in protection

Abstract

We identified subgroup specific protective epitopes represented by the amino acid regions 174–187 and 171–187 of the G glycoproteins from respiratory syncytial virus (RSV), subgroups A and B. Mice immunized with coupled synthetic peptides corresponding to either the region 174–187 containing a Cys186 → Ser substitution or to the native region 171–187 were completely resistant to RSV infection but only to the respective virus. The protective activities of the peptides 174–187 were dependent on the Cys186 → Ser substitution. In addition, a recombinant protein representing the region 125–203 of the A subgroup G glycoprotein expressed in Escherichia coli was capable without further treatment to completely protect animals against RSV subgroup A infection. We show that the combinations of cysteinyl residues (positions 173, 176, 182, and 186) retained within either synthetic peptides or the recombinant protein G 125–203 greatly influenced their protective activities. This indicates that the region 171–187 is essential for the protection conferred by the G 125–203 protein. Furthermore, our results strongly suggest that the peptides' and recombinant protein's potencies are a function of a loop-like structure which is stabilized by intramolecular disulfide linkages between Cys176–Cys182 and Cys173–Cys186. This is further supported by the observation that chemical blocking of the sulfidryl groups in synthetic peptides completely eliminated their protective activity.