Respiratory syncytial virus is the most common cause of lower respiratory tract diesase in young children worldwide. The F glycoprotein of this virus is one of the targets of a protective immune response; however, despite significant conservation in the F glycoprotein and the developement of anti-F antibodies following natural infection, immunity is incomplete and repeated infections with viruses of the homologous or heterologous subtype occur despite high levels of neutralizing antibody. These findings suggest that intratypic antigenic idifferences in the F glycoprotein might be able to convey an epidemiological advantage during the course of natural infection. In order to study intratypic antigenic variation and the role it plays in the development of a protective immune response, we have characterized clinical isolates that vary in fusion epitopes. Although these viruses bind to and are neutralized by F-antibodies, fusion of infected cells is not inhibited by the presence of antibody to the F glycoprotein. Sequence analysis of the envelope glycoproteins has identified several amino acids that may contribute to the ability of these viruses to cause fusion. During serial passage of the clinical isolates in VERO cells we have been able to produce viruses that have gained reactivity with the fusion inhibiting antibody. Sequence analysis of these passaged viruses should help to identify the specific changes that contribute to escape from fusion inhibition. Additional studies have been done to compare F expression and epitope density for small plaque and large plaque viruses in order to understand factors that regulate fusion activity.
