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Influenza A Virus Field Surveillance at a Swine-Human Interface.
mSphere ( IF 4.8 ) Pub Date : 2020-02-05 , DOI: 10.1128/msphere.00822-19
Benjamin L Rambo-Martin 1 , Matthew W Keller 2 , Malania M Wilson 3 , Jacqueline M Nolting 4 , Tavis K Anderson 5 , Amy L Vincent 5 , Ujwal R Bagal 1 , Yunho Jang 3 , Elizabeth B Neuhaus 3 , C Todd Davis 3 , Andrew S Bowman 4 , David E Wentworth 3 , John R Barnes 6
Affiliation  

While working overnight at a swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, Nanopore sequenced 13 IAV genomes from samples we collected, and predicted in real time that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current prepandemic candidate vaccine viruses (CVVs). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 h after unpacking the mobile lab. Exhibition swine are a known source for zoonotic transmission of IAV to humans and pose a potential pandemic risk. Genomic analyses of IAV in swine are critical to understanding this risk, the types of viruses circulating in swine, and whether current vaccines developed for use in humans would be predicted to provide immune protection. Nanopore sequencing technology has enabled genome sequencing in the field at the source of viral outbreaks or at the bedside or pen-side of infected humans and animals. The acquired data, however, have not yet demonstrated real-time, actionable public health responses. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes, A(H1N1), A(H3N2), and A(H1N2). Analysis of the hemagglutinin (HA) sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 of these viruses and the most closely related CVV. As an exercise in pandemic preparedness, all sequences were emailed to CDC collaborators who initiated the development of a synthetically derived CVV.IMPORTANCE Swine are influenza virus reservoirs that have caused outbreaks and pandemics. Genomic characterization of these viruses enables pandemic risk assessment and vaccine comparisons, though this typically occurs after a novel swine virus jumps into humans. The greatest risk occurs where large groups of swine and humans comingle. At a large swine exhibition, we used Nanopore sequencing and on-site analytics to interpret 13 swine influenza virus genomes and identified an influenza virus cluster that was genetically highly varied to currently available vaccines. As part of the National Strategy for Pandemic Preparedness exercises, the sequences were emailed to colleagues at the CDC who initiated the development of a synthetically derived vaccine designed to match the viruses at the exhibition. Subsequently, this virus caused 14 infections in humans and was the dominant U.S. variant virus in 2018.

中文翻译:

猪-人界面的甲型流感病毒现场监测。

在猪展上通宵工作时,我们发现了猪中甲型流感病毒 (IAV) 的爆发,Nanopore 对我们收集的样本中的 13 个 IAV 基因组进行了测序,并实时预测这些病毒由于之间的基因不匹配而对人类构成新的风险。病毒和当前大流行前候选疫苗病毒(CVV)。我们开发并使用了名为 Mia(移动流感分析)的便携式 IAV 测序和分析平台,在打开移动实验室大约 18 小时后完成并表征全长共有基因组。展览猪是 IAV 向人类传播人畜共患病的已知来源,并构成潜在的大流行风险。猪 IAV 的基因组分析对于了解这种风险、猪体内传播的病毒类型以及当前开发的用于人类的疫苗是否有望提供免疫保护至关重要。纳米孔测序技术使得在病毒爆发源头或受感染的人类和动物的床边或围栏旁进行基因组测序成为可能。然而,所获得的数据尚未证明实时、可操作的公共卫生应对措施。Mia 系统迅速从 A(H1N1)、A(H3N2) 和 A(H1N2) 三种亚型中鉴定出三种遗传上不同的猪 IAV 谱系。对 A(H1N2) 病毒的血凝素 (HA) 序列的分析发现,这些病毒的 HA1 与最密切相关的 CVV 之间存在 > 30 个氨基酸差异。作为大流行防范的一项练习,所有序列都通过电子邮件发送给 CDC 合作者,他们发起了合成衍生的 CVV 的开发。 重要性 猪是流感病毒的储存库,曾导致爆发和大流行。这些病毒的基因组特征使得大流行风险评估和疫苗比较成为可能,尽管这通常发生在新型猪病毒感染人类之后。最大的风险发生在大群猪和人类聚集的地方。在一次大型猪展上,我们使用纳米孔测序和现场分析解读了 13 种猪流感病毒基因组,并鉴定了一个与现有疫苗在基因上存在很大差异的流感病毒簇。作为国家大流行防范战略的一部分,这些序列通过电子邮件发送给疾病预防控制中心的同事,他们发起了一种合成疫苗的开发,旨在与展览上的病毒相匹配。随后,该病毒引起了14人感染,成为2018年美国的主要变种病毒。
更新日期:2020-02-06
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