The interaction of cellular protein ANP32A with influenza A virus polymerase component PB2 promotes vRNA synthesis

被引:11
作者
Wei, Xiuli [1 ,2 ]
Liu, Zhixin [1 ]
Wang, Jingjie [1 ]
Yang, Ruiping [3 ]
Yang, Jing [1 ]
Guo, Yang [1 ]
Tan, Huabing [2 ]
Chen, Hongying [4 ]
Liu, Qiang [5 ]
Liu, Long [1 ,2 ]
机构
[1] Hubei Univ Med, Sch Basic Med Sci, Shiyan 442000, Hubei, Peoples R China
[2] Hubei Univ Med, Renmin Hosp, Dept Infect Dis, Shiyan 442000, Hubei, Peoples R China
[3] Hubei Univ Med, Biomed Res Inst, Shiyan 442000, Hubei, Peoples R China
[4] Northwest A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China
[5] China Three Gorges Univ, Yichang Cent Peoples Hosp, Coll Clin Med Sci 1, Yichang 443000, Peoples R China
关键词
STIMULATORY HOST FACTOR; VIRAL MESSENGER-RNAS; STRUCTURAL INSIGHTS; CRYSTAL-STRUCTURE; PA PROTEIN; TRANSCRIPTION; RIBONUCLEOPROTEIN; ENDONUCLEASE; REPLICATION; MECHANISMS;
D O I
10.1007/s00705-018-04139-z
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The subunits PA, PB1, and PB2 of influenza A virus RNA polymerase are essential for efficient viral RNA synthesis and virus replication because of their role in recruiting multiple nuclear proteins. ANP32A is an acidic leucine-rich nuclear phosphoprotein 32 (ANP32) family member and a crucial cellular protein that determines the species specificity of the influenza virus RNA polymerase activity. However, how ANP32A modulates polymerase activity remains largely unknown. In this study, we showed that viral RNA synthesis was increased in A549 cells overexpressing ANP32A and decreased after treatment with ANP32A RNAi. This decrease in RNA synthesis was reversed by rescued ANP32A expression. The results of docking modeling, co-immunoprecipitation, and yeast two-hybrid assays showed that PB2 was the only subunit of the three that interacted with ANP32A. The C-terminal portion of ANP32A and the middle domains (residues 307-534) of PB2 were required for PB2-ANP32A interaction. Glu189 and Glu196 in ANP32A and Gly450 and Gln447 in PB2 were essential for interaction between ANP32A and PB2. These residues were located in conserved regions of the ANP32A or PB2 protein sequences. These data suggest that ANP32A is recruited to the polymerase through direct interaction with PB2 via critical amino acid residue interactions and promotes viral RNA synthesis. Our findings might provide new insights into the molecular mechanisms underlying influenza virus RNA synthesis and replication in infected human cells.
引用
收藏
页码:787 / 798
页数:12
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