Molecular Evolution of Respiratory Syncytial Virus Fusion Gene, Canada, 2006–2010

Jesse Papenburg, Julie Carbonneau, Marie-Ève Hamelin, Sandra Isabel, Xavier Bouhy, Najwa Ohoumanne, Pierre Déry, Bosco A. Paes, Jacques Corbeil, Michel G. Bergeron, Gaston De Serres, and Guy Boivin

Author affiliations: McGill University Health Centre, Montréal, Québec, Canada (J. Papenburg); Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada (J. Papenburg, J. Carbonneau, M.-È. Hamelin, S. Isabel, X. Bouhy, P. Déry, J. Corbeil, M.G. Bergeron, G. Boivin); Institut National de Santé Publique du Québec, Québec (N. Ohoumanne, G. De Serres); McMaster Children’s Hospital, Hamilton, Ontario, Canada (B.A. Paes)

Abstract

To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSV-positive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006–2010. Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.

Human respiratory syncytial virus (RSV) is the most common cause of acute respiratory tract infections (RTIs) and a major cause of hospital admission and death among children <5 years of age worldwide (1). Risk for severe RSV-associated illness is highest among children born prematurely or with chronic medical disorders (2). Palivizumab immunoprophylaxis is the only available measure to prevent severe RSV disease.
The RSV fusion (RSV-F) surface glycoprotein mediates virus fusion to host cells. It is a major antigenic determinant that elicits neutralizing antibodies and cytotoxic T-lymphocyte immunity (3). Palivizumab (MedImmune, Gaithersburg, MD, USA) is a humanized mouse monoclonal antibody that inhibits RSV-F by binding to a defined epitope (residues 262–276) (4,5). Palivizumab immunoprophylaxis is recommended for the prevention of serious lower RTIs caused by RSV in children at high risk (6). RSV strains with mutations in key amino acid residues within the palivizumab binding site are resistant to this antibody (7–9); however, little is known about the prevalence of such mutations in clinical samples. Furthermore, despite its role in RSV pathogenesis, immunity, and prevention strategies, few data on RSV-F molecular evolution are available (10,11) because previous phylogenetic studies have focused on the RSV-G glycoprotein (12,13). Therefore, we monitored evolutionary changes in RSV-F, particularly potential resistance mutations in the palivizumab binding site, among strains from children who did and did not receive palivizumab.