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Journal of Virology, May 2004, p. 4675-4683, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4675-4683.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Molecular Evolution and Circulation Patterns of Human Respiratory Syncytial Virus Subgroup A: Positively Selected Sites in the Attachment G Glycoprotein

Kalina T. Zlateva, Philippe Lemey, Anne-Mieke Vandamme, and Marc Van Ranst*

Laboratory of Clinical & Epidemiological Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium

Received 28 June 2003/ Accepted 16 January 2004

Human respiratory syncytial virus (HRSV) is the most common etiological agent of acute lower respiratory tract disease in infants and can cause repeated infections throughout life. In this study, we have analyzed nucleotide sequences encompassing 629 bp at the carboxy terminus of the G glycoprotein gene for HRSV subgroup A strains isolated over 47 years, including 112 Belgian strains isolated over 19 consecutive years (1984 to 2002). By using a maximum likelihood method, we have tested the presence of diversifying selection and identified 13 positively selected sites with a posterior probability above 0.5. The sites under positive selection correspond to sites of O glycosylation or to amino acids that were previously described as monoclonal antibody-induced in vitro escape mutants. Our findings suggest that the evolution of subgroup A HRSV G glycoprotein is driven by immune pressure operating in certain codon positions located mainly in the second hypervariable region of the ectodomain. Phylogenetic analysis revealed the prolonged cocirculation of two subgroup A lineages among the Belgian population and the possible extinction of three other lineages. The evolutionary rate of HRSV subgroup A isolates was estimated to be 1.83 x 10–3 nucleotide substitutions/site/year, projecting the most recent common ancestor back to the early 1940s.

* Corresponding author. Mailing address: Laboratory of Clinical and Epidemiological Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, University of Leuven Medical School, Minderbroedersstraat 10, BE-3000 Leuven, Belgium. Phone: 32-16-347908. Fax: 32-16-347900. E-mail: marc.vanranst{at}uz.kuleuven.ac.be.

Journal of Virology, May 2004, p. 4675-4683, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4675-4683.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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