title: 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 G125-203 greatly influenced their protective activities. This indicates that the region 171-187 is essential for the protection conferred by the G125-203 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.
authors.affiliation: Institut Armand-Frappier, Centre de recherche en virologie, Laval des Rapides, Québec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Simard
authors.forename: F
authors.initials: F
authors.lastname: Nadon
authors.forename: C
authors.initials: C
authors.lastname: Séguin
authors.forename: N N
authors.initials: NN
authors.lastname: Thien
authors.forename: H
authors.initials: H
authors.lastname: Binz
authors.forename: J
authors.initials: J
authors.lastname: Basso
authors.forename: J F
authors.initials: JF
authors.lastname: Laliberté
authors.forename: M
authors.initials: M
authors.lastname: Trudel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D003545:Cysteine / Q000276:immunology* / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D015707:HN Protein; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000145:classification / Q000276:immunology*; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D015707:HN Protein; D010455:Peptides; D013438:Sulfhydryl Compounds; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D003545:Cysteine