Table_1_Analysis of circulating respiratory syncytial virus A strains in Shanghai, China identified a new and increasingly prevalent lineage within the dominant ON1 genotype.XLSX

Respiratory syncytial virus A (RSV-A) is one of the commonest pathogens causing acute respiratory tract infections in infants and children globally. The currently dominant circulating genotype of RSV-A, ON1, was first detected in Shanghai, China in 2011, but little data are available regarding its subsequent circulation and clinical impact here. In this work, we analyzed RSV-A infection in a cohort of patients hospitalized for acute respiratory infections in Shanghai Children’s Hospital, and RSV-A was detected in ~10% of these cases. RSV-A G gene sequencing revealed that all successfully sequenced strains belonged to ON1 genotype, but in phylogenetic analysis, the majority of these sequences formed a clade separate from the four previously established lineages within ON1. The new lineage, denoted ON1-5, was supported by phylogenetic analyses using additional G gene sequences from RSV-A strains isolated in Shanghai and elsewhere. ON1-5 first appeared in 2015 in China and the Netherlands, and has since spread to multiple continents and gained dominance in Asia. In our cohort, ON1-5 was not associated with markedly different clinical presentations compared to other ON1 lineages. ON1-5 strains are characterized by four amino acid variations in the two mucin-like regions of G protein, and one variation (N178G) within the highly conserved CCD domain that is involved in receptor binding. These data highlight the continuous evolution of RSV-A, and suggest the possibility of the virus acquiring variations in domains traditionally considered to be conserved for fitness gain.

呼吸道合胞病毒A亚型（Respiratory syncytial virus A, RSV-A）是全球范围内引发婴幼儿急性呼吸道感染的最常见病原体之一。目前全球流行的RSV-A优势基因型ON1于2011年首次在我国上海被检出，但针对该基因型后续在我国的传播情况与临床影响，相关研究数据仍较为匮乏。本研究针对上海儿童医院收治的急性呼吸道感染住院患者队列开展RSV-A感染分析，结果显示约10%的病例检出RSV-A。对RSV-A的G基因进行测序后发现，所有成功完成测序的毒株均属于ON1基因型；但系统发育分析显示，其中多数毒株形成了一个独立进化支，区别于ON1基因型此前已明确的4个谱系。该新谱系被命名为ON1-5，通过对上海及其他地区分离的RSV-A毒株额外G基因序列进行系统发育分析，该分类得到了验证。ON1-5谱系于2015年首次在我国与荷兰被发现，此后传播至多个大洲，并在亚洲地区占据流行优势地位。在本研究队列中，ON1-5谱系毒株的临床表征与其他ON1谱系毒株并无显著差异。ON1-5毒株的特征为G蛋白的两个黏蛋白样区域存在4处氨基酸变异，且在参与受体结合的高度保守CCD结构域内存在1处变异（N178G）。本研究数据凸显了RSV-A的持续进化特性，同时提示该病毒可能在以往认为保守的结构域中获得变异，以提升自身适配性。