Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute-ICB-II, University of São Paulo, São Paulo, Brazil.
PLoS One. 2012;7(10):e41953. doi: 10.1371/journal.pone.0041953. Epub 2012 Oct 15.
Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide.
METHODOLOGY/PRINCIPAL FINDINGS: Here 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/SIGNIFICANCE: Genotypes 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.
人类呼吸道合胞病毒(HRSV)是导致全球儿童呼吸道感染的主要病原体之一。
方法/主要发现:本研究通过对包含多个基因型的 HRSV 两大主要群组 A 和 B(n=1983)进行全面分析,呈现了 50 年来(1956-2006 年)HRSV 种群动态的复杂模式。HRSV 的循环模式显示了一系列共同循环谱系的扩张和波动,以 HRSVA 为主导。GB3 插入(GB3 Insert)的 60 个核苷酸插入导致 G 糖蛋白的阳性选择氨基酸取代,而其他基因型在种群增长和减少时都获得了取代,因此可能反映了免疫选择表位与追踪替代位点的联系在疫苗设计中具有重要意义。分析表明,巴西存在不同 HRSV 基因型的共同循环和优势,表明该病毒全年存在。在巴西,GA2 和 GA5 是 HRSV 爆发的主要罪魁祸首,直到最近,GB3 Insert 变得高度流行。使用贝叶斯方法,我们通过几个推断的迁移路径确定了基因型的扩散模式。
结论/意义:基因型在各大洲和邻近地区传播。至关重要的是,基因型在任何给定地区也会持续存在很长时间,这可能与重新感染普通人群有关,而与季节性爆发无关。