title: Adaptive mutation PB2 D701N promotes nuclear import of influenza vRNPs in mammalian cells.
abstract: The segmented genome of influenza viruses is translocated into the nucleus to initiate transcription and replication. The gene segments are present as viral ribonucleoprotein (vRNP) particles composed of RNA, multiple copies of the nucleoprotein (NP), and the polymerase subunits PB1, PB2 and PA. The PB2 subunit and each NP monomer contain a nuclear localisation signal (NLS) that binds to importin-α. To throw light on the role of the NLSs of NP and PB2 in nuclear transport, we have analysed the effect of mutation D701N, responsible for the exposure of the NLS domain of PB2, on the intracellular localisation of vRNPs. We show that exposure of PB2 NLS significantly enhances the amount of vRNPs present in the nucleus. These observations suggest that entry of vRNPs into the nucleus depends on controlled interplay of the NLSs of PB2 and NP with the nuclear import machinery.
authors.affiliation: Institute of Virology, Philipps Universität, Marburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Sediri
authors.affiliation: Institute of Virology, Philipps Universität, Marburg, Germany.
authors.forename: Folker
authors.initials: F
authors.lastname: Schwalm
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie, Hamburg, Germany.
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
authors.affiliation: Institute of Virology, Philipps Universität, Marburg, Germany. Electronic address: klenk@staff.uni-marburg.de.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics*; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000235:genetics; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D012261:Ribonucleoproteins / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D019913:Nuclear Localization Signals; C057027:PB2 protein, Influenzavirus A; D012367:RNA, Viral; D012261:Ribonucleoproteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Influenza virus; Nuclear import; PB2