Abstract
BackgroundHuman respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide.Methodology/Principal FindingsHere through a comprehensive analysis of the two major HRSV groups A and B (n = 1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956–2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes.Conclusions/SignificanceGenotypes spread across continents and between neighboring areas. Crucially, genotypes also remained at any given region for extended periods, independent of seasonal outbreaks possibly maintained by re-infecting the general population.
Highlights
Human respiratory syncytial virus (HRSV) causes serious respiratory tract infections in infants, elderly and immunocompromised adults [1,2,3,4]
It is worthwhile to consider that a lack of sampling of any given HRSV genotype does not mean that the lineage itself may have necessarily died out, since it may be experiencing cryptic circulation in the regions that we examined, or it may be still circulating in other localities that we did not obtain samples from
The dynamics profile of the GB3 Insert indicated a clear pattern of population growth concurrent with amino acid replacements at positively selected codons of the immunogenic G glycoprotein
Summary
Human respiratory syncytial virus (HRSV) causes serious respiratory tract infections in infants, elderly and immunocompromised adults [1,2,3,4]. HRSV epidemics are associated with climate patterns and occur annually in late autumn and winter in temperate climates, and within the rainy season in tropical countries [5,6]. It is estimated that 64 million HRSV infections occur annually, resulting in 160,000 deaths (Initiative for Vaccine Research: respiratory syncytial virus, World Health Organization http://www.who.int/vaccine_research/diseases/ ari/en/index3.html, update September 2009). Children are susceptible to repeated HRSV infections and to developing severe disease [7,8]. Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide
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