生物
神经氨酸酶
上位性
抗原漂移
血凝素(流感)
病毒
抗原变异
人口
病毒进化
甲型流感病毒
实验进化
进化生物学
遗传学
基因
病毒学
基因组
人口学
社会学
作者
Tongyu Liu,Yiquan Wang,Timothy J.C. Tan,Nicholas C. Wu,Christopher B. Brooke
标识
DOI:10.1016/j.chom.2022.09.003
摘要
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.
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