Nelson Martha I, Wentworth David E, Culhane Marie R, Vincent Amy L, Viboud Cecile, LaPointe Matthew P, Lin Xudong, Holmes Edward C, Detmer Susan E
Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA
J. Craig Venter Institute, Rockville, Maryland, USA.
J Virol. 2014 Sep 1;88(17):10110-9. doi: 10.1128/JVI.01080-14. Epub 2014 Jun 25.
The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus--A/sw/Saskatchewan/02903/2009(H3N2)--has likely circulated undetected in swine for at least 7 years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931 to 2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least 1 year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, suggesting an association between the acquisition of swine-origin internal genes via reassortment and the adaptation of human influenza viruses to new swine hosts. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multihost ecology of influenza and the disease threats that swine and humans pose to each other.
The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus evolves in these animals hosts. While the importance of reassortment in generating genetically diverse influenza viruses in swine is well documented, the role of human-to-swine transmission has not been as intensively studied. Through a large-scale sequencing effort, we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least 7 years. In addition, we demonstrate that human-to-swine transmission has occurred frequently on a global scale over the past decades but that there is little persistence of human virus internal gene segments in swine.
甲型流感病毒跨越物种屏障的能力对人类和动物健康构成持续威胁。了解人猪界面对于理解具有大流行潜力的病毒如何在猪宿主中进化尤为重要。我们对2002年至2011年从北美猪身上收集的141种流感病毒的基因组进行了测序，并鉴定出一种猪病毒，它拥有源自人类季节性A/H3N2病毒的所有八个基因组片段。分子钟分析表明，这种病毒——A/sw/萨斯喀彻温省/02903/2009（H3N2）——可能已在猪中未被检测到地传播了至少7年。为了了解历史背景，我们对1931年至2013年期间全球收集的另外1404个甲型猪流感病毒全基因组序列进行了全面的系统发育分析。在此期间，人传猪的情况频繁发生，自1965年以来，有20次人类季节性甲型流感病毒的离散引入在猪中显示出持续的传播至少1年。值得注意的是，在猪中检测到的源自人类的血凝素（H1和H3）和神经氨酸酶（特别是N2）片段的比例远高于六个内部基因片段，这表明通过重配获得猪源内部基因与人类流感病毒适应新的猪宿主之间存在关联。在基因组水平上进一步了解人类病毒适应猪以及反之亦然的适应性限制，对于理解流感复杂的多宿主生态学以及猪和人类相互构成的疾病威胁至关重要。
2009年甲型H1N1大流行病毒的猪源凸显了了解甲型流感病毒如何在这些动物宿主中进化的重要性。虽然重排在猪中产生基因多样化的流感病毒方面的重要性已有充分记录，但人传猪的作用尚未得到如此深入的研究。通过大规模测序工作，我们鉴定出一种完全源自人类的新型流感病毒，它已在猪中未被检测到地传播了至少7年。此外，我们证明在过去几十年中，人传猪在全球范围内频繁发生，但人类病毒内部基因片段在猪中几乎没有持久性。
