Data associated with the publication: The impact of human H3N2 influenza virus reassortment during 2017-18 on increased influenza cases and disease severity: enhanced virus replication and neuraminidase antibody immune evasion

During the 2017-18 influenza season in the United States, there was a high incidence of influenza illness and mortality. However, no apparent mutations were identified in the HA gene segment of dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. Clinical samples from the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 influenza seasons were sequenced to target influenza A virus. Phylogenetic trees were constructed based on viral whole genome sequences. Representative viral isolates of the two seasons were characterized in immortalized cell lines and human nasal epithelial cell cultures, and demographic data and clinical outcomes of patients were analyzed. Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titer compared to the parental 3C.2a2 and 3C.2a1 viruses, which may have contributed to the increased severity. The reassortant re3C.3a was able to infect an older population more effectively compared to the parental 3C.3a, perhaps through evasion of preexisting NA antibodies. Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, co-circulating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information may help inform future vaccine development and public health policies.

2017-2018年美国流感季期间，流感发病率与死亡率居高不下。然而，主流H3N2病毒的血凝素（Hemagglutinin, HA）基因片段并未检出明显突变，该季流感的严重程度无法仅归因于疫苗匹配度不佳。本研究针对约翰·霍普金斯流感研究与监测卓越中心（Johns Hopkins Center of Excellence for Influenza Research and Surveillance）网络在2016-2017及2017-2018流感季采集的临床样本，针对甲型流感病毒进行测序。基于病毒全基因组序列构建系统发育树。对两个流感季的代表性病毒分离株开展永生化细胞系及人类鼻上皮细胞培养实验，并分析患者的人口统计学数据与临床转归。研究观测到独特的H3N2重配事件，致使2017-2018季出现两种优势毒株：HA分支3C.2a2与3C.3a，二者均携带源自HA分支3C.2a1病毒的基因片段，形成全新的基因片段组合。与亲本3C.2a2及3C.2a1毒株相比，重配毒株re3C.2a2的复制动力学更快、峰值滴度更高，这或为该季流感严重程度上升的诱因之一。重配毒株re3C.3a相较亲本3C.3a毒株，可更高效地感染老年人群，这一现象可能与其逃避预先存在的神经氨酸酶（Neuraminidase, NA）抗体有关。本研究结果表明，2017-2018年美国流感季的严重程度上升，部分源于两种共同循环的H3N2亚型内重配病毒——相较于亲本毒株，二者均具备适合度优势。该研究结果可为未来疫苗研发及公共卫生政策制定提供参考依据。