title: Influenza A virus nucleoprotein targets subnuclear structures.
abstract: The Influenza A virus nucleoprotein (NP) is the major protein component of the genomic viral ribonucleoprotein (vRNP) complexes, which are the replication- and transcription-competent units of Influenza viruses. Early during infection, NP mediates import of vRNPs into the host cell nucleus where viral replication and transcription take place; also newly synthesized NP molecules are targeted into the nucleus, enabling coreplicational assembly of progeny vRNPs. NP reportedly acts as regulatory factor during infection, and it is known to be involved in numerous interactions with host cell proteins. Yet, the NP-host cell interplay is still poorly understood. Here, we report that NP significantly interacts with the nuclear compartment and displays distinct affinities for different subnuclear structures. NP subnuclear behavior was studied by expression of fluorescent NP fusion proteins - including obligate monomeric NP - and site-specific fluorescence photoactivation measurements. We found that NP constructs accumulate in subnuclear domains frequently found adjacent to or overlapping with promyelocytic leukemia bodies and Cajal bodies. Targeting of NP to Cajal bodies could further be demonstrated in the context of virus infection. We hypothesize that by targeting functional nuclear organization, NP might either link viral replication to specific cellular machinery or interfere with host cell processes.
authors.affiliation: IRI Life Sciences, Department of Biology, Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.|Department of Veterinary Medicine, Institute of Virology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Höfer
authors.affiliation: IRI Life Sciences, Department of Biology, Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Jolmes
authors.affiliation: IRI Life Sciences, Department of Biology, Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Haralampiev
authors.affiliation: Department of Veterinary Medicine, Institute of Virology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Veit
authors.affiliation: IRI Life Sciences, Department of Biology, Molecular Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D004285:Dogs; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D007251:Influenza, Human / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D009698:Nucleoproteins / Q000378:metabolism*; D021381:Protein Transport; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D009698:Nucleoproteins; D014764:Viral Proteins