Centers for Disease Control and Prevention, Influenza Division, Atlanta, Georgia, USA.
Association of Public Health Laboratories, Silver Springs, Maryland, USA.
J Virol. 2020 Dec 22;95(2). doi: 10.1128/JVI.01066-20.
Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the U.S. swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as "swine-origin" or "human-origin" due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as "swine-origin" variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 hemagglutinin (HA) and neuraminidase (NA) genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source, future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses. Influenza virus infects a wide range of hosts, resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and nonhuman hosts, resulting in human and nonhuman origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza.
季节性流感病毒在人群中的传播可导致类似人流感病毒在美国猪群中持续循环。虽然有些反向人畜共患病病毒在猪群中适应并成为地方流行，但新生的反向人畜共患病可能导致病毒检测结果难以归类为“猪源”或“人源”，因为循环病毒的遗传相似性。这就是自 2009 年大流行以来，因多次发生反向人畜共患病事件而在猪群中检测到的人源甲型 H1N1 流感 2009 （pdm09）病毒的情况。我们报告了两例人感染源自猪宿主的甲型 H1N1pdm09 病毒的病例，并根据系统进化分析和序列比较方法将其归类为“猪源”变异流感病毒。对两例病例病毒基因组的系统进化分析显示，这些病毒是由 A（H1N1）pdm09 血凝素（HA）和神经氨酸酶（NA）基因组成的重组体，其遗传组合源自三重重配内部基因盒。后续调查确定，其中一人在发病前一周有直接接触猪的情况，另一人没有报告猪接触史。通过对变异病毒与猪流感基因组的全基因组序列比较，解决了猪源 A（H1N1）变异病例的问题。然而，如果重组不导致获得猪相关基因，并且无法从暴露源获得猪病毒基因组序列，则未来的病例可能无法识别。我们已经开发了一种能够进行最大似然分析、基于 k-mer 的集合差异算法和随机森林算法的流程，以识别血凝素基因中的猪相关序列，从而区分人源和猪源 A（H1N1）pdm09 病毒。流感病毒感染范围广泛，导致从无症状病例到严重肺炎和死亡的各种疾病。病毒可以在人类和非人类宿主之间转移，导致在新宿主中循环的人源和非人源病毒。在这项工作中，我们已经确定了首例由猪源甲型 H1N1pdm09 病毒引起的人类感染病例。这表明这些病毒不仅在猪宿主中循环，而且还在继续进化，并与以前流行的人源流感病毒区分开来。区分人源和猪源病毒的技术的发展对于流感病毒的持续监测是必要的。我们表明，独特的遗传特征可以区分循环的猪相关株和循环的人相关株甲型 H1N1pdm09，并且这些特征可用于增强对猪源流感的监测。
