title: CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2.
abstract: NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Liu
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.forename: Ziduo
authors.initials: Z
authors.lastname: Liu
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D028884:Karyopherins / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D049790:Nuclear Export Signals; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D004265:DNA Helicases; D028884:Karyopherins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D049790:Nuclear Export Signals; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D017361:Viral Nonstructural Proteins; D000097606:Exportin 1 Protein; C556232:NS2 protein, influenza virus A; C115322:CHD3 protein, human