title: Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection.
abstract: Many viruses deliver their genomes into the host cell nucleus for replication. However, the size restrictions of the nuclear pore complex (NPC), which regulates the passage of proteins, nucleic acids, and solutes through the nuclear envelope, require virus capsid uncoating before viral DNA can access the nucleus. We report a microtubule motor kinesin-1-mediated and NPC-supported mechanism of adenovirus uncoating. The capsid binds to the NPC filament protein Nup214 and kinesin-1 light-chain Klc1/2. The nucleoporin Nup358, which is bound to Nup214/Nup88, interacts with the kinesin-1 heavy-chain Kif5c to indirectly link the capsid to the kinesin motor. Kinesin-1 disrupts capsids docked at Nup214, which compromises the NPC and dislocates nucleoporins and capsid fragments into the cytoplasm. NPC disruption increases nuclear envelope permeability as indicated by the nuclear influx of large cytoplasmic dextran polymers. Thus, kinesin-1 uncoats viral DNA and compromises NPC integrity, allowing viral genomes nuclear access to promote infection.
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Switzerland.
authors.forename: Sten
authors.initials: S
authors.lastname: Strunze
authors.forename: Martin F
authors.initials: MF
authors.lastname: Engelke
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Puntener
authors.forename: Karin
authors.initials: K
authors.lastname: Boucke
authors.forename: Sibylle
authors.initials: S
authors.lastname: Schleich
authors.forename: Michael
authors.initials: M
authors.lastname: Way
authors.forename: Philipp
authors.initials: P
authors.lastname: Schoenenberger
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Burckhardt
authors.forename: Urs F
authors.initials: UF
authors.lastname: Greber
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000257:Adenoviridae Infections / Q000378:metabolism* / Q000821:virology; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019065:Virus Assembly
chemical_list: C488101:KIF5B protein, human; C000715688:KLC1 protein, human; D028861:Nuclear Pore Complex Proteins; D016547:Kinesins