title: An investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture.
abstract: Human respiratory syncytial virus isolates have previously been shown to exhibit resistance to neutralization by anti-fusion glycoprotein antibodies that is lost on passage in cell culture. Early passage resistant and late passage susceptible stocks of two virus isolates from different epidemics were cloned by plaque purification. Early passage stocks of both isolates yielded predominantly neutralization resistant clones while late passage stocks yielded predominantly susceptible clones. On further characterization of resistant and susceptible clones, resistant virus yields were lower and they were relatively resistant to both neutralization and fusion inhibition by anti-F murine monoclonal antibodies and were also resistant to neutralization by human sera and by Palivizumab. The full genome of resistant and susceptible clones from one of the isolates was sequenced. Four differences, confirmed by sequencing sister clones, were found between resistant and susceptible clones, one in each of the SH, G, F, and L genes.
authors.affiliation: The Institute of Cellular Medicine, The University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Hiriote
authors.forename: E L Michael
authors.initials: EL
authors.lastname: Gias
authors.forename: S H
authors.initials: SH
authors.lastname: Welsh
authors.forename: G L
authors.initials: GL
authors.lastname: Toms
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D016679:Genome, Viral; D006801:Humans; D051379:Mice; D009154:Mutation; D009500:Neutralization Tests; D012367:RNA, Viral / Q000235:genetics; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012367:RNA, Viral; D014760:Viral Fusion Proteins
keywords: Palivizumab; gene sequence; quasi-species