Increased susceptibility of human respiratory syncytial virus to neutralization by anti-fusion protein antibodies on adaptation to replication in cell culture.
Subgroup A respiratory syncytial viruses present in respiratory secretions and low passage level cell culture isolates were found to be markedly less susceptible to neutralization with monoclonal antibodies (MAbs) to the F glycoprotein than the cell culture adapted A2 virus strain. Low passage virus isolates collected over a 20 year period and belonging to several sub-group A lineages were refractory to neutralization with antibodies recognizing two major neutralizing antigenic sites located sub-terminally at opposite ends of the F(1) glycoprotein sub-unit. On further passage in cell culture, virus isolates exhibited both increased infectivity titers and increased susceptibility to neutralization by antibodies to both antigenic sites. The consensus nucleotide sequence of the membrane associated proteins M and of the SH, G and F glycoprotein genes, and their intergenic regions were compared for neutralization resistant and susceptible stocks of one virus strain, R17532. No changes were observed in the known monoclonal antibody epitopes on the F glycoprotein. In line with this, the increase in susceptibility was not found to be associated with any increased binding of monoclonal antibody to isolated F glycoprotein in a BIAcore assay, thus excluding the possibility that passage in cell culture selected for viruses with mutations in the antibody binding sites. M and SH genes were conserved but a number of sites in the G and F glycoprotein genes were found to vary on adaptation to cell culture suggesting that change in susceptibility to neutralization was associated with a change in the prevalent quasispecies present in the virus population. The genetic basis of phenotypic change in susceptibility remains to be determined.
Marsh
R
R
The School of Clinical Medical Sciences, The Medical School, The University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Connor
A
A
Gias
E
E
Toms
G L
GL
D000914:Antibodies, Viral / Q000276:immunology*; D018929:Cell Culture Techniques; D004252:DNA Mutational Analysis; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D009305:Nasopharynx / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D012692:Serial Passage; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D000914:Antibodies, Viral; D000939:Epitopes; D014760:Viral Fusion Proteins; D014764:Viral Proteins