title: NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.
abstract: Influenza remains a serious worldwide public health problem. After infection, viral genomic RNA is replicated in the nucleus and packed into viral ribonucleoprotein, which will then be exported to the cytoplasm via a cellular chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and budding. However, the nuclear export mechanism of influenza virus remains controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1-knockdown cells exhibit decreased viral replication kinetics and nuclear accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C-terminal region of NP. These findings reveal a distinct mechanism for nuclear export of the influenza virus and identify the NXT1/NP interaction as a potential target for antiviral drug development.
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan. nopporn.chutiwitoonchai@riken.jp.
authors.forename: Nopporn
authors.initials: N
authors.lastname: Chutiwitoonchai
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, Wako, Saitama 351-0198, Japan. aida@riken.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D004285:Dogs; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D028884:Karyopherins / Q000378:metabolism*; D019590:Nucleocapsid Proteins; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*; D019065:Virus Assembly; D057074:Virus Release; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D019590:Nucleocapsid Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014758:Viral Core Proteins; D000097606:Exportin 1 Protein; C048842:NP protein, Influenza A virus; C498546:NXT1 protein, human
keywords: CRM1; Influenza A virus; NP; NXT1; nuclear export