当前位置: X-MOL 学术Emerg. Microbes Infect. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Insights into species-specific regulation of ANP32A on the mammalian-restricted influenza virus polymerase activity.
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2019-01-01 , DOI: 10.1080/22221751.2019.1676625
Zhenwei Bi 1 , Hongliu Ye 1 , Xingbo Wang 2, 3 , An Fang 1 , Tianqi Yu 1, 2, 3 , Liping Yan 1 , Jiyong Zhou 2, 3
Affiliation  

The ANP32A is responsible for mammalian-restricted influenza virus polymerase activity. However, the mechanism of ANP32A modulation of polymerase activity remains poorly understood. Here, we report that chicken ANP32A (chANP32A) -X1 and -X2 stimulated mammalian-restricted PB2 627E polymerase activity in a dose-dependent manner. Distinct effects of ANP32A constructs suggested that the 180VK181 residues within chANP32A-X1 are necessary but not sufficient to stimulate PB2 627E polymerase activity. The PB2 N567D, T598V, A613V or F636L mutations promoted PB2 627E polymerase activity and chANP32A-X1 showed additive effects, providing further support that species-specific regulation of ANP32A might be only relevant with the PB2 E627K mutation. Rescue of cycloheximide-mediated inhibition showed that ANP32A is species-specific for modulation of vRNA but not mRNA and cRNA, demonstrating chANP32A-X1 compensated for defective cRNPs produced by PB2 627E virus in mammalian cells. The promoter mutations of cRNA enhanced the restriction of PB2 627E polymerase in mammalian cells, which could be restored by chANP32A-X1, indicating that ANP32A is likely to regulate the interaction of viral polymerase with RNA promoter. Coimmunoprecipitation showed that ANP32A did not affect the primary cRNPs assembly. We propose a model that chANP32A-X1 regulates PB2 627E polymerase for suitable interaction with cRNA promoter for vRNA replication.

中文翻译:

深入了解ANP32A对哺乳动物限制的流感病毒聚合酶活性的物种特异性调控。

ANP32A负责哺乳动物限制性流感病毒聚合酶的活性。但是,ANP32A调节聚合酶活性的机制仍然知之甚少。在这里,我们报告鸡ANP32A(chANP32A)-X1和-X2以剂量依赖的方式刺激了哺乳动物限制性PB2 627E聚合酶活性。ANP32A构建体的不同作用表明,chANP32A-X1中的180VK181残基是必需的,但不足以刺激PB2 627E聚合酶活性。PB2 N567D,T598V,A613V或F636L突变促进了PB2 627E聚合酶活性,而chANP32A-X1显示出累加效应,进一步证明了ANP32A的物种特异性调控可能仅与PB2 E627K突变有关。环己酰亚胺介导的抑制作用的挽救表明,ANP32A对vRNA的调节具有物种特异性,但对mRNA和cRNA的调节却不是,这表明chANP32A-X1可以补偿PB2 627E病毒在哺乳动物细胞中产生的缺陷性cRNPs。cRNA的启动子突变增强了哺乳动物细胞中PB2 627E聚合酶的限制,可通过chANP32A-X1恢复,表明ANP32A可能调节病毒聚合酶与RNA启动子的相互作用。免疫共沉淀显示ANP32A不会影响主要的cRNPs装配。我们提出了一个模型,chANP32A-X1调节PB2 627E聚合酶,使其与cRNA启动子相互作用以进行vRNA复制。cRNA的启动子突变增强了哺乳动物细胞中PB2 627E聚合酶的限制,可通过chANP32A-X1恢复,表明ANP32A可能调节病毒聚合酶与RNA启动子的相互作用。免疫共沉淀显示ANP32A不会影响主要的cRNPs装配。我们提出了一个模型,chANP32A-X1调节PB2 627E聚合酶,使其与cRNA启动子相互作用以进行vRNA复制。cRNA的启动子突变增强了哺乳动物细胞中PB2 627E聚合酶的限制,可通过chANP32A-X1恢复,表明ANP32A可能调节病毒聚合酶与RNA启动子的相互作用。免疫共沉淀显示ANP32A不会影响主要的cRNPs装配。我们提出了一个模型,chANP32A-X1调节PB2 627E聚合酶,使其与cRNA启动子相互作用以进行vRNA复制。
更新日期:2019-11-01
down
wechat
bug