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

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.

Conflict of interest statement

Competing Interests: Li-Min Huang is a PLOS ONE Editorial Board member, but this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. Li-Min Huang, MD, PhD.

Figures

Figure 1. Variability in the fusion protein region of RSV isolated from 2000–2011.

1A shows P-distance for nucleotides and 1B shows P-distance for amino acid.

Figure 2. Phylogenetic analysis of the RSV partial F gene (nt 110–869).

The tree topology was constructed using the neighbor-joining method. Only bootstrap values greater than 75% (1,000 bootstrap replicates) are shown. Panels A and B show details for RSV-A and RSV-B. Red and blue texts indicate the Taiwanese RSV-A and RSV-B strains, respectively. The scale bar represents the evolutionary distance.

Figure 3. Bayesian skyline plot derived from alignment of the RSV partial F gene sequences in Taiwan.

The x axis is in units of years before 2010, and the y axis represents the effective population size of the virus (i.e. the number of genomes effectively contributing to the next generation). The thick solid black line is the estimated median, and the pale gray areas show the upper and lower bounds of the 95% HDP interval.