title: The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export.
abstract: In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs.
authors.affiliation: From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and.
authors.forename: Linda
authors.initials: L
authors.lastname: Brunotte
authors.affiliation: From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and.
authors.forename: Joe
authors.initials: J
authors.lastname: Flies
authors.affiliation: From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and.
authors.forename: Hardin
authors.initials: H
authors.lastname: Bolte
authors.affiliation: From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and.
authors.forename: Peter
authors.initials: P
authors.lastname: Reuther
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX 3RE, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: Vreede
authors.affiliation: From the Institute for Virology, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany and martin.schwemmle@uniklinik-freiburg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwemmle
mesh_terms: D021581:Active Transport, Cell Nucleus; D057809:HEK293 Cells; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C488936:M1 protein, Influenza A virus; D029543:Nucleocytoplasmic Transport Proteins; D012367:RNA, Viral; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins
keywords: Influenza Virus; Protein Export; Ribonucleoprotein (RNP); Viral Polymerase; Viral Protein