Loss of conserved cysteine residues in the attachment (G) glycoprotein of two human respiratory syncytial virus escape mutants that contain multiple A-G substitutions (hypermutations).
Two escape mutants (R10c/1 and R10c/10) of the human respiratory syncytial (RS) virus Long strain were selected after serial passage in the presence of monoclonal antibody c793 directed against the G glycoprotein. This antibody recognizes an epitope which is shared by all viruses of the two antigenic subgroups in which human RS virus isolates have been subdivided. The mutant viruses had lost most of the G protein conserved and subgroup-specific epitopes but maintained the strain-variable epitopes. The two mutants had 10 or 11 nucleotide changes in the central region of the G protein gene when compared to the Long sequence, and almost all of those changes were different between the two mutants. The majority of the nucleotide changes involved A-G transitions (U-C in the positive sense) that resulted in amino acid substitutions. Each mutant had a total of six amino acid changes, and the changes were different between the two mutants. Unexpectedly, each mutant lost one of the four conserved cysteines of the G protein, and a different cysteine (Cys 182 or 186) was lost in each mutant. They are, in fact, the first reported RS viruses with only three cysteines in the G protein ectodomain. The genetic mechanism that generated the escape mutants and its relevance for the natural history of RS virus are discussed.
Rueda
P
P
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
García-Barreno
B
B
Melero
J A
JA
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D001483:Base Sequence; D017124:Conserved Sequence; D003545:Cysteine / Q000235:genetics; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D015707:HN Protein; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017354:Point Mutation; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000276:immunology; D012692:Serial Passage; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D003545:Cysteine