title: An important amino acid in nucleoprotein contributes to influenza A virus replication by interacting with polymerase PB2.
abstract: The nucleoprotein (NP) of influenza A virus plays a critical role in the formation of viral ribonucleoprotein (vRNP) complex. However, it remains unclear which key residues in NP are associated with the assembly of vRNP and contribute to virus replication. Here, a highly conserved aspartic acid at residue 88 (D88) of NP was identified by molecular docking of NP with the Fv region of a broad-spectrum anti-NP mAb 19C10 and further demonstrated to be an important residue contributes to the RNP activity, virus growth in MDCK cells and replication in lungs of infected mice by comparing recombinant wild-type A/WSN/1933 virus to the mutant virus that contains an alanine instead of aspartic acid at NP residue 88. D88 was also predicted to interact with PB2 by molecular docking and further verified by immunoprecipitation. These findings provide new information for understanding the interaction between NP and other polymerase subunits in virus replication.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Gui
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Guo
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Kang
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China. Electronic address: yxchen2008@xmu.edu.cn.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectiou Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China. Electronic address: nsxia@xmu.edu.cn.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D009980:Influenza A virus / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D009698:Nucleoproteins; C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Docking; Epitope; Influenza A virus; Interaction; Nucleoprotein; Replication; vRNP complex