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. 2004 May;78(9):4675-83.
doi: 10.1128/jvi.78.9.4675-4683.2004.

Molecular evolution and circulation patterns of human respiratory syncytial virus subgroup a: positively selected sites in the attachment g glycoprotein

Kalina T Zlateva  1 , Philippe Lemey, Anne-Mieke Vandamme, Marc Van Ranst
Affiliations
Free PMC article

Molecular evolution and circulation patterns of human respiratory syncytial virus subgroup a: positively selected sites in the attachment g glycoprotein

Kalina T Zlateva et al. J Virol. 2004 May.
Free PMC article

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Phylogenetic tree of HRSV-A strains as computed with paup4b10. The nucleotide sequences of the G glycoprotein gene of the Belgian isolates were compared with those from Madrid (MAD), Montevideo (MON), Seoul (SEL), West Virginia (WV), and Birmingham (BIR) with the original nomenclature RSB89-642 (BIR642/88-89), RSB89-1734 (BIR1734/88-89), and RSB89-6190 (BIR6190/89-90) and compared with those from New York (NY) with original nomenclature CH17 (NY/CH17/93), CH09 (NY/CH09/93), CH57 (NY/CH57/94), CH34 (NY/CH34/94), and the reference strains Long (USA/Long/56), A2 (AUS/A2/61), and RSS-2 (UK/RSS-2/76). The Long strain was used as the outgroup sequence in the tree. The numbers at the internal nodes represent the number of bootstrap probabilities, as determined for 1,000 iterations by the neighbor-joining method. Only bootstrap values greater than 77% are shown. The italicized numbers in brackets at the terminal nodes correspond to the numbers of identical sequences. The genetic clusters obtained in the analysis are indicated by the square brackets and the designations GA1, GA2, GA4, GA5, and BE/A1.
FIG. 2.
FIG. 2.
Posterior probabilities of site classes along the G protein ectodomain region under the discrete model M3. This model assumes three classes of sites in the gene: positive sites (▪), neutral sites (□), and negative sites (formula image). Positively selected amino acid sites with posterior probabilities above 50% are indicated according to the Long strain. Amino acid variability, measured by entropy (Hi), is plotted to the second y axis.
FIG. 3.
FIG. 3.
Linear root-to-tip regression plot.
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References

    1. Akerlind, B., and E. Norrby. 1986. Occurrence of respiratory syncytial virus subtypes A and B strains in Sweden. J. Med. Virol. 19:241-247. - PubMed
    1. Anderson, L. J., J. C. Hierholzer, C. Tsou, R. M. Hendry, B. F. Fernie, Y. Stone, and K. McIntosh. 1985. Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. J. Infect. Dis. 151:626-633. - PubMed
    1. Cane, P. A. 2001. Molecular epidemiology of respiratory syncytial virus. Rev. Med. Virol. 11:103-116. - PubMed
    1. Cane, P. A. 1997. Analysis of linear epitopes recognised by the primary human antibody response to a variable region of the attachment (G) protein of respiratory syncytial virus. J. Med. Virol. 51:297-304. - PubMed
    1. Cane, P. A., and C. R. Pringle. 1995. Molecular epidemiology of respiratory syncytial virus: a review of the use of reverse transcription-polymerase chain reaction in the analysis of genetic variability. Electrophoresis 16:329-333. - PubMed

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