Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Emory University, Atlanta, Georgia, USA.
J Virol. 2018 Jul 31;92(16). doi: 10.1128/JVI.00665-18. Print 2018 Aug 15.
While several swine-origin influenza A H3N2 variant (H3N2v) viruses isolated from humans prior to 2011 have been previously characterized for their virulence and transmissibility in ferrets, the recent genetic and antigenic divergence of H3N2v viruses warrants an updated assessment of their pandemic potential. Here, four contemporary H3N2v viruses isolated during 2011 to 2016 were evaluated for their replicative ability in both and in mammalian models as well as their transmissibility among ferrets. We found that all four H3N2v viruses possessed similar or enhanced replication capacities in a human bronchial epithelium cell line (Calu-3) compared to a human seasonal influenza virus, suggestive of strong fitness in human respiratory tract cells. The majority of H3N2v viruses examined in our study were mildly virulent in mice and capable of replicating in mouse lungs with different degrees of efficiency. In ferrets, all four H3N2v viruses caused moderate morbidity and exhibited comparable titers in the upper respiratory tract, but only 2 of the 4 viruses replicated in the lower respiratory tract in this model. Furthermore, despite efficient transmission among cohoused ferrets, recently isolated H3N2v viruses displayed considerable variance in their ability to transmit by respiratory droplets. The lack of a full understanding of the molecular correlates of virulence and transmission underscores the need for close genotypic and phenotypic monitoring of H3N2v viruses and the importance of continued surveillance to improve pandemic preparedness. Swine-origin influenza viruses of the H3N2 subtype, with the hemagglutinin (HA) and neuraminidase (NA) derived from historic human seasonal influenza viruses, continue to cross species barriers and cause human infections, posing an indelible threat to public health. To help us better understand the potential risk associated with swine-origin H3N2v viruses that emerged in the United States during the 2011-2016 influenza seasons, we use both and models to characterize the abilities of these viruses to replicate, cause disease, and transmit in mammalian hosts. The efficient respiratory droplet transmission exhibited by some of the H3N2v viruses in the ferret model combined with the existing evidence of low immunity against such viruses in young children and older adults highlight their pandemic potential. Extensive surveillance and risk assessment of H3N2v viruses should continue to be an essential component of our pandemic preparedness strategy.
虽然在 2011 年之前从人类中分离出来的几种猪源甲型 H3N2 变异（H3N2v）病毒已经对其在雪貂中的毒力和传染性进行了描述，但 H3N2v 病毒最近的遗传和抗原分化需要对其大流行潜力进行更新评估。在这里，我们评估了 2011 年至 2016 年期间分离的四种当代 H3N2v 病毒在哺乳动物模型中的复制能力以及在雪貂中的传播能力。我们发现，与季节性人类流感病毒相比，所有四种 H3N2v 病毒在人类支气管上皮细胞系（Calu-3）中均具有相似或增强的复制能力，这表明其在人类呼吸道细胞中具有很强的适应性。我们研究中检查的大多数 H3N2v 病毒在小鼠中为低毒力，并能以不同的效率在小鼠肺部中复制。在雪貂中，所有四种 H3N2v 病毒均引起中度发病，并在上呼吸道中表现出相当的滴度，但在该模型中，只有 4 种病毒中的 2 种在呼吸道下部复制。此外，尽管在共同饲养的雪貂中可以有效传播，但最近分离的 H3N2v 病毒在通过呼吸道飞沫传播的能力方面表现出相当大的差异。对毒力和传播的分子相关性缺乏充分的了解，突显了需要密切监测 H3N2v 病毒的基因型和表型，并强调需要继续进行监测以改善大流行的准备工作。具有源自历史上人类季节性流感病毒的血凝素（HA）和神经氨酸酶（NA）的 H3N2 亚型猪源流感病毒继续跨越物种屏障并引起人类感染，对公共卫生构成不可磨灭的威胁。为了帮助我们更好地了解在美国出现的与 2011-2016 年流感季节相关的猪源 H3N2v 病毒相关的潜在风险，我们使用 和 模型来描述这些病毒在哺乳动物宿主中复制，引起疾病和传播的能力。一些 H3N2v 病毒在雪貂模型中表现出的高效呼吸道飞沫传播能力，加上在幼儿和老年人中对这些病毒的免疫力低下的现有证据，突出了它们的大流行潜力。对 H3N2v 病毒的广泛监测和风险评估应继续成为我们大流行准备策略的重要组成部分。
