Antigenic structure of the human respiratory syncytial virus G glycoprotein and relevance of hypermutation events for the generation of antigenic variants.
A set of monoclonal antibodies (MAbs) specific for the attachment (G) glycoprotein of a recently isolated strain of human respiratory syncytial virus (HRSV) is described. Antibody reactivity with a series of HRSV isolates belonging to antigenic groups A and B identified three epitope categories: (i) strain-specific or variable epitopes that were present in a limited set of viruses from the same antigenic group, (ii) group-specific epitopes shared by viruses from the same antigenic group and (iii) conserved epitopes present in all HRSV isolates. Sequence analysis of escape mutants was used to map relevant antigenic sites of the G glycoprotein. Strain-specific epitopes were located preferentially in the variable C-terminal third of the G polypeptide, in agreement with previous studies of the Long strain. However, a new strain-specific epitope was mapped into another variable region, N-terminal to the cluster of cysteines in the G protein ectodomain. In contrast, the group-specific and conserved epitopes were located in the central conserved region of the G protein primary structure. These results, together with previous analysis of the Long strain, provide a detailed antigenic map of the HRSV attachment protein. Some mutants selected with group-specific antibodies contain multiple A-G substitutions (hypermutations) and lack one or two of the four cysteines which are conserved in all HRSV isolates. The genetic mechanism implicated in the generation of the hypermutated viruses and its relevance for the natural history of HRSV are discussed.
Martínez
I
I
Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Dopazo
J
J
Melero
J A
JA
D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D018604:Epitope Mapping; D015707:HN Protein; D006801:Humans; D009154:Mutation; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G