Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection

Sten Strunze, Martin F. Engelke, I. Hsuan Wang, Daniel Puntener, Karin Boucke, Sibylle Schleich, Michael Way, Philipp Schoenenberger, Christoph J. Burckhardt, Urs F. Greber

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)210-223
Number of pages14
JournalCell Host and Microbe
Volume10
Issue number3
DOIs
StatePublished - Sep 15 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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