Joseph Udayan, Vijaykrishna Dhanasekaran, Smith Gavin J D, Su Yvonne C F
Programme in Emerging Infectious Diseases Duke-NUS Medical School Singapore.
Department of Microbiology Biomedicine Discovery Institute Monash University Melbourne Vic. Australia.
Evol Appl. 2017 Oct 24;11(4):534-546. doi: 10.1111/eva.12536. eCollection 2018 Apr.
An H1N1 subtype influenza A virus with all eight gene segments derived from wild birds (including mallards), ducks and chickens, caused severe disease outbreaks in swine populations in Europe beginning in 1979 and successfully adapted to form the European avian-like swine (EA-swine) influenza lineage. Genes of the EA-swine lineage that are clearly segregated from its closest avian relatives continue to circulate in swine populations globally and represent a unique opportunity to study the adaptive process of an avian-to-mammalian cross-species transmission. Here, we used a relaxed molecular clock model to test whether the EA-swine virus originated through the introduction of a single avian ancestor as an entire genome, followed by an analysis of host-specific selection pressures among different gene segments. Our data indicated independent introduction of gene segments via transmission of avian viruses into swine followed by reassortment events that occurred at least 1-4 years prior to the EA-swine outbreak. All EA-swine gene segments exhibit greater selection pressure than avian viruses, reflecting both adaptive pressures and relaxed selective constraints that are associated with host switching. Notably, we identified key amino acid mutations in the viral surface proteins (H1 and N1) that play a role in adaptation to new hosts. Following the establishment of EA-swine lineage, we observed an increased frequency of intrasubtype reassortment of segments compared to the earlier strains that has been associated with adaptive amino acid replacements, disease severity and vaccine escape. Taken together, our study provides key insights into the adaptive changes in viral genomes following the transmission of avian influenza viruses to swine and the early establishment of the EA-swine lineage.
一种甲型H1N1流感病毒的所有八个基因片段均源自野生鸟类（包括绿头鸭）、鸭和鸡，自1979年起在欧洲猪群中引发了严重疾病爆发，并成功适应形成了欧洲禽源样猪（EA-猪）流感谱系。EA-猪谱系的基因与其最亲近的禽类亲属明显分离，继续在全球猪群中传播，这为研究禽流感病毒向哺乳动物跨物种传播的适应过程提供了独特机会。在此，我们使用宽松分子钟模型来测试EA-猪病毒是否起源于单个禽类祖先作为完整基因组的引入，随后分析不同基因片段之间宿主特异性选择压力。我们的数据表明，通过禽流感病毒传播到猪群，随后在EA-猪疫情爆发前至少1至4年发生重配事件，基因片段是独立引入的。所有EA-猪基因片段均表现出比禽流感病毒更大的选择压力，这既反映了与宿主转换相关的适应性压力，也反映了放松的选择限制。值得注意的是，我们在病毒表面蛋白（H1和N1）中鉴定出关键氨基酸突变，这些突变在适应新宿主方面发挥作用。在EA-猪谱系建立之后，我们观察到与早期毒株相比，片段的亚型内重配频率增加，这与适应性氨基酸替换、疾病严重程度和疫苗逃逸有关。综上所述，我们的研究为禽流感病毒传播到猪群后病毒基因组的适应性变化以及EA-猪谱系的早期建立提供了关键见解。
