Circulation of HRSV in Belgium: From Multiple Genotype Circulation to Prolonged Circulation of Predominant Genotypes

Molecular surveillance of HRSV in Belgium for 15 consecutive seasons (1996–2011) revealed a shift from a regular 3-yearly cyclic pattern, into a yearly alternating periodicity where HRSV-B is replaced by HRSV-A. Phylogenetic analysis for HRSV-A demonstrated the stable circulation of GA2 and GA5, with GA2 being dominant over GA5 during 5 consecutive seasons (2006–2011). We also identified 2 new genotype specific amino acid mutations of the GA2 genotype (A122 and Q156) and 7 new GA5 genotype specific amino acid mutations (F102, I108, T111, I125, D161, S191 and L217). Several amino acid positions, all located in the second hypervariable region of HRSV-A were found to be under positive selection. Phylogenetic analysis of HRSV-B showed the circulation of GB12 and GB13, where GB13 represented 100% of the isolated strains in 4 out of 5 consecutive seasons (2007–2011). Amino acids under positive selection were all located in the aminoterminal hypervariable region of HRSV-B, except one amino acid located in the conserved region. The genotype distribution within the HRSV-B subgroup has evolved from a co-circulation of multiple genotypes to the circulation of a single predominant genotype. The Belgian GB13 strains circulating since 2006, all clustered under the BAIV branch and contained several branch specific amino acid substitutions. The demographic history of genotypes GA2, GA5 and GB13 demonstrated a decrease in the total GA2 and GA5 population size, coinciding with the global expansion of the GB13 population. The emergence of the GB13 genotype resulted in a newly established balance between the predominant genotypes.对1996至2011年连续15个流行季节的比利时呼吸道合胞病毒（HRSV）开展分子监测，结果显示其流行周期从规律的3年周期性循环模式转变为年度交替循环模式，在此过程中HRSV-B亚型被HRSV-A亚型取代。针对HRSV-A的系统发育分析表明，GA2与GA5基因型持续流行，且GA2在2006至2011年连续5个季节中均占据主导地位。本研究还鉴定出GA2基因型的2个新基因型特异性氨基酸突变位点（A122与Q156），以及GA5基因型的7个新基因型特异性氨基酸突变位点（F102、I108、T111、I125、D161、S191及L217）。研究发现多个位于HRSV-A第二高变区的氨基酸位点处于正选择压力之下。针对HRSV-B的系统发育分析显示，其流行株包含GB12与GB13两种基因型，其中GB13在2007至2011年连续5个季节中的4个季节内占分离株总数的100%。除1个位于保守区的氨基酸位点外，其余处于正选择压力下的氨基酸位点均位于HRSV-B的氨基端高变区。HRSV-B亚型内的基因型分布已从多基因型共同流行演变为单一优势基因型主导流行的格局。2006年以来在比利时地区流行的GB13毒株均聚类于BAIV分支，并携带多个分支特异性氨基酸替换。对GA2、GA5及GB13基因型的种群动态历史分析显示，GA2与GA5的种群总规模呈下降趋势，这与GB13种群的全球扩张相吻合。GB13基因型的出现促成了优势基因型之间新的平衡格局。