Molecular epidemiology and phylodynamics of the human respiratory syncytial virus fusion protein in northern Taiwan

PLoS One. 2013 May 29;8(5):e64012. doi: 10.1371/journal.pone.0064012. Print 2013.

Abstract

Background and aims: The glycoprotein (G protein) and fusion protein (F protein) of respiratory syncytial virus (RSV) both show genetic variability, but few studies have examined the F protein gene. This study aimed to characterize the molecular epidemiology and phylodynamics of the F protein gene in clinical RSV strains isolated in northern Taiwan from 2000-2011.

Methods: RSV isolates from children presenting with acute respiratory symptoms between July 2000 and June 2011 were typed based on F protein gene sequences. Phylogeny construction and evaluation were performed using the neighbor-joining (NJ) and maximum likelihood (ML) methods. Phylodynamic patterns in RSV F protein genes were analyzed using the Bayesian Markov Chain Monte Carlo framework. Selection pressure on the F protein gene was detected using the Datamonkey website interface.

Results: From a total of 325 clinical RSV strains studied, phylogenetic analysis showed that 83 subgroup A strains (RSV-A) could be further divided into three clusters, whereas 58 subgroup B strains (RSV-B) had no significant clustering. Three amino acids were observed to differ between RSV-A and -B (positions 111, 113, and 114) in CTL HLA-B*57- and HLA-A*01-restricted epitopes. One positive selection site was observed in RSV-B, while none was observed in RSV-A. The evolution rate of the virus had very little change before 2000, then slowed down between 2000 and 2005, and evolved significantly faster after 2005. The dominant subtypes of RSV-A in each epidemic were replaced by different subtypes in the subsequent epidemic.

Conclusions: Before 2004, RSV-A infections were involved in several small epidemics and only very limited numbers of strains evolved and re-emerged in subsequent years. After 2005, the circulating RSV-A strains were different from those of the previous years and continued evolving through 2010. Phylodynamic pattern showed the evolutionary divergence of RSV increased significantly in the recent 5 years in northern Taiwan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Cell Line
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • Evolution, Molecular
  • Female
  • Genetic Variation
  • HLA-A1 Antigen / immunology
  • HLA-A1 Antigen / metabolism
  • HLA-B Antigens / immunology
  • HLA-B Antigens / metabolism
  • Hep G2 Cells
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Epidemiology
  • Molecular Sequence Data
  • Monte Carlo Method
  • Phylogeny*
  • Respiratory Syncytial Virus Infections / epidemiology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Virus, Human / classification*
  • Respiratory Syncytial Virus, Human / genetics
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Taiwan / epidemiology
  • Viral Fusion Proteins / classification*
  • Viral Fusion Proteins / genetics

Substances

  • Epitopes, T-Lymphocyte
  • F protein, human respiratory syncytial virus
  • HLA-A*01:01 antigen
  • HLA-A1 Antigen
  • HLA-B Antigens
  • HLA-B57 antigen
  • Viral Fusion Proteins

Associated data

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Grants and funding

This study was supported by grants MMH 9783 from Mackay Memorial Hospital, Taipei, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.