Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015
Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015
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DOI：
10.1128/jvi.00134-16
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发表时间：
2016-05-01
影响因子：
5.4
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
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作者：
Belser, Jessica A.;Creager, Hannah M.;Tumpey, Terrence M.
迄今为止，人类感染H7N9流感病毒的三波已经结束，但只有第一波（2013年3月至9月期间分离的）病毒在哺乳动物模型中得到了广泛研究。虽然第二波和第三波病毒在遗传学和抗原性上保持密切联系，但即使是细微的分子变化也会使哺乳动物的毒力发生重大变化。为了确定2013年至2015年期间从人类分离的H7N9病毒是否保持了2013年分离株中首次发现的表型，我们评估了从人类分离的第一波，第二波和第三波H7N9病毒在小鼠和雪貂中引起疾病以及在雪貂中传播的能力。与第一波病毒类似，2013年至2015年的H7N9病毒在小鼠中具有高度感染性，其致死率与经过充分研究的A/Anhui/1/2013病毒相当。第二波和第三波病毒在雪貂中引起中度疾病，有效地传播给共同饲养的幼稚接触动物，并通过呼吸道飞沫表现出有限的传播性。所有H7N9病毒在人支气管上皮细胞中有效复制，在检测的H7N9病毒之间鉴定出pH融合阈值的细微变化。我们的研究结果表明，尽管自2013年首次发现以来遗传多样性和地理分布有所增加，但H7N9病毒在哺乳动物中保持了致病性表型，并继续对公共卫生构成直接威胁。
Three waves of human infection with H7N9 influenza viruses have concluded to date, but only viruses within the first wave (isolated between March and September 2013) have been extensively studied in mammalian models. While second-and third-wave viruses remain closely linked phylogenetically and antigenically, even subtle molecular changes can impart critical shifts in mammalian virulence. To determine if H7N9 viruses isolated from humans during 2013 to 2015 have maintained the phenotype first identified among 2013 isolates, we assessed the ability of first-, second-, and third-wave H7N9 viruses isolated from humans to cause disease in mice and ferrets and to transmit among ferrets. Similar to first-wave viruses, H7N9 viruses from 2013 to 2015 were highly infectious in mice, with lethality comparable to that of the well-studied A/Anhui/1/2013 virus. Second-and third-wave viruses caused moderate disease in ferrets, transmitted efficiently to cohoused, naive contact animals, and demonstrated limited transmissibility by respiratory droplets. All H7N9 viruses replicated efficiently in human bronchial epithelial cells, with subtle changes in pH fusion threshold identified between H7N9 viruses examined. Our results indicate that despite increased genetic diversity and geographical distribution since their initial detection in 2013, H7N9 viruses have maintained a pathogenic phenotype in mammals and continue to represent an immediate threat to public health.