PB2蛋白E627K/V突变增强禽流感病毒对哺乳动物适应性研究进展

Advances on E627K/V Mutation of PB2 Protein Enhancing the Adaptability of Avian Influenza Virus to Mammals

禽流感病毒(Avian influenza virus,AIV)跨越种间屏障感染哺乳动物后须获得适应性突变才能在哺乳动物体内高水平复制,PB2蛋白E627K/V突变(PB2-E627K或PB2-E627V)在其中发挥关键促进作用。在多种亚型AIV感染人病例中,PB2-E627K突变占比均显著增加,该突变主要通过增强病毒在哺乳动物细胞中的聚合酶活性和突破宿主限制性因子的阻碍作用促进AIV在哺乳动物细胞中的复制。H9N2亚型AIV感染人病例中PB2-E627V的占比较高,且该突变在其他亚型人源毒株中同样高频率出现,该突变同样可增强AIV在哺乳动物细胞中的复制,增强在哺乳动物中的致病性和传播性,但其促进作用一般不如E627K显著,E627V被认为是AIV适应哺乳动物的中间状态。文章分析了不同宿主来源的AIV中PB2蛋白第627位氨基酸的多态性,总结了该位点适应哺乳动物的分子机制,强调了加强对禽源和哺乳动物源AIV的分子标记监测对阻止未来可能发生的大流行具有重要意义。

Avian influenza virus(AIV)requires adaptive mutations for efficient replication within mammalian hosts,with the PB2 protein E627K/V mutation(PB2-E627K or PB2-E627V)playing crucial facilitating roles.In human cases of infection with various AIV subtypes,the prevalence of PB2-E627K mutation significantly increases,primarily enhancing viral polymerase activity in mammalian cells and overcoming host restrictive factors to promote AIV replication.Conversely,in human cases of H9N2 AIV infection,PB2-E627V mutation prevalence is notably higher,and this mutation occurs at similarly high frequencies in other subtypes of human-origin strains.PB2-E627V similarly enhances AIV replication in mammalian cells,augmenting pathogenicity and transmissibility in mammals,although its facilitating effect is generally less pronounced than that of E627K.E627V is considered an intermediate state in AIV adaptation to mammals.This article analyzed the polymorphism of PB2 protein amino acid 627 in AIV from different host sources,summarized the molecular mechanisms underlying adaptation to mammals at this site,and emphasized the importance of enhancing molecular surveillance of avian and mammalian-origin AIV strains for preventing potential future pandemics.