The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with neuraminidase.
The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with neuraminidase.
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流感A病毒血凝素的进化潜力受到与神经氨酸酶的上皮相互作用的高度限制。
DOI：
10.1016/j.chom.2022.09.003
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发表时间：
2022-10-12
影响因子：
30.3
通讯作者：
Brooke, Christopher B.
中科院分区：
文献类型：
--
作者：
Liu, Tongyu;Wang, Yiquan;Tan, Timothy J. C.;Wu, Nicholas C.;Brooke, Christopher B.
甲型流感病毒（IAV）血凝素（HA）基因的抗原进化限制了有效控制病毒在人群中传播的努力。为了理解HA抗原进化的机制，通常会单独检查HA基因。这可能忽略了平衡HA受体结合活性与病毒神经氨酸酶（NA）的受体破坏活性以维持病毒适应性的重要性。我们假设，需要保持功能平衡NA显着约束HA的进化潜力。我们使用深度突变扫描，并表明NA活性的变化通过调节HA的整体突变鲁棒性来显著重塑HA适应性景观。与此一致，我们观察到不同的NA背景支持在中和抗体压力下HA逃逸变体的不同库的出现。我们的研究结果揭示了一个关键的作用，节间上位性影响HA基因的进化潜力。流感病毒血凝素（HA）的抗原性漂移对疫苗的有效性提出了挑战。预测抗原漂移通常是单独检查HA。Liu等人表明HA与其功能对应物神经氨酸酶之间的功能相互作用重塑了HA的适应性景观，并导致HA的独特抗原逃逸特征。
Antigenic evolution of the influenza A virus (IAV) hemagglutinin (HA) gene limits efforts to effectively control the spread of the virus in the population. Efforts to understand the mechanisms governing HA antigenic evolution typically examine the HA gene in isolation. This can ignore the importance of balancing HA receptor-binding activities with the receptor-destroying activities of the viral neuraminidase (NA) to maintain viral fitness. We hypothesize that the need to maintain functional balance with NA significantly constrains the evolutionary potential of the HA. We use deep mutational scanning and show that variation in NA activity significantly reshapes the HA fitness landscape by modulating the overall mutational robustness of HA. Consistent with this, we observe that different NA backgrounds support the emergence of distinct repertoires of HA escape variants under neutralizing antibody pressure. Our results reveal a critical role for intersegment epistasis in influencing the evolutionary potential of the HA gene. Antigenic drift of influenza hemagglutinin (HA) poses great challenge to vaccine effectiveness. Predicting the antigenic drift typically examinates HA in isolation. Liu et al. showed the functional interaction between HA and its functional counterpart neuraminidase reshaped the fitness landscape of HA and leaded to distinct antigenic escape profile of HA.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
48
作者：
Fowler, Douglas M.;Fields, Stanley
通讯作者：
Fields, Stanley
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
6.7
作者：
Doud, Michael B.;Hensley, Scott E.;Bloom, Jesse D.
通讯作者：
Bloom, Jesse D.
影响因子：
30.3
作者：
Das, Suman R.;Hensley, Scott E.;Yewdell, Jonathan W.
通讯作者：
Yewdell, Jonathan W.