Adaptation of avian influenza virus to a swine host.
Adaptation of avian influenza virus to a swine host.
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DOI：
10.1093/ve/vex007
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发表时间：
2017-01
期刊：
影响因子：
5.3
通讯作者：
Tiley LS
中科院分区：
文献类型：
--
作者：
Bourret V;Lyall J;Frost SDW;Teillaud A;Smith CA;Leclaire S;Fu J;Gandon S;Guérin JL;Tiley LS
致病性RNA病毒进入新宿主的出现可能对牲畜和公共卫生产生严重后果。在这里，我们的特点是在以前的研究中观察到的病毒遗传变化，实验适应鸭流感病毒的现场分离猪呼吸道细胞。在这种适应过程中选择了既存突变和新生突变。我们比较了适应病毒的体外生长动力学与原始菌株，以及所有可能的rerectants使用反向遗传学。这种完全析因设计表明，病毒基因片段参与了对病毒适应度的复杂上位性相互作用，包括负上位和符号上位。我们还确定了两个点突变的位置67和113的HA2亚基的血凝素蛋白赋予一个快速生长表型的幼稚禽流感病毒在猪细胞。这些HA2突变增强pH依赖性HA介导的膜融合。一个全球H1最大似然系统发育分析，结合全面的祖先重建和测试的方向选择，证实了该领域的相关性HA2的位置113的突变。最值得注意的是，这种突变与H1“禽流感样”猪流感谱系的建立有关，被认为是最有可能导致下一次人类流感大流行。这种研究病毒适应遗传学的多学科方法为导致流感在新宿主物种中出现的潜在过程提供了独特的见解，并为未来的监测和功能研究确定了具体目标。
The emergence of pathogenic RNA viruses into new hosts can have dramatic consequences for both livestock and public health. Here we characterize the viral genetic changes that were observed in a previous study which experimentally adapted a field isolate of duck influenza virus to swine respiratory cells. Both pre-existing and de novo mutations were selected during this adaptation. We compare the in vitro growth dynamics of the adapted virus with those of the original strain as well as all possible reassortants using reverse genetics. This full factorial design showed that viral gene segments are involved in complex epistatic interactions on virus fitness, including negative and sign epistasis. We also identify two point mutations at positions 67 and 113 of the HA2 subunit of the hemagglutinin protein conferring a fast growth phenotype on the naïve avian virus in swine cells. These HA2 mutations enhance the pH dependent, HA-mediated membrane fusion. A global H1 maximum-likelihood phylogenetic analysis, combined with comprehensive ancestry reconstruction and tests for directional selection, confirmed the field relevance of the mutation at position 113 of HA2. Most notably, this mutation was associated with the establishment of the H1 ‘avian-like’ swine influenza lineage, regarded as the most likely to cause the next influenza pandemic in humans. This multidisciplinary approach to study the genetics of viral adaptation provides unique insights on the underlying processes leading to influenza emergence in a new host species, and identifies specific targets for future surveillance and functional studies.
影响因子：
3.5
作者：
Bourret V;Lyall J;Ducatez MF;Guérin JL;Tiley L
通讯作者：
Tiley L