Influenza virus uses transportin 1 for vRNP debundling during cell entry

Yasuyuki Miyake, Jeremy J. Keusch, Laure Decamps, Hung Ho-Xuan, Sho Iketani, Heinz Gut, Ulrike Kutay, Ari Helenius, Yohei Yamauchi*

*Corresponding author for this work

Research output: Contribution to journalLetter (Academic Journal)peer-review

39 Citations (Scopus)
452 Downloads (Pure)


Influenza A virus is a pathogen of great medical impact. To develop novel antiviral strategies, it is essential to understand the molecular aspects of virus–host cell interactions in detail. During entry, the viral ribonucleoproteins (vRNPs) that carry the RNA genome must be released from the incoming particle before they can enter the nucleus for replication. The uncoating process is facilitated by histone deacetylase 6 (ref.1). However, the precise mechanism of shell opening and vRNP debundling is unknown. Here, we show that transportin 1, a member of the importin-β family proteins, binds to a PY-NLS2 sequence motif close to the amino terminus of matrix protein (M1) exposed during acid priming of the viral core. It promotes the removal of M1 and induces disassembly of vRNP bundles. Next, the vRNPs interact with importin-α/β and enter the nucleus. Thus, influenza A virus uses dual importin-βs for distinct steps in host cell entry.

Original languageEnglish
Pages (from-to)578-586
Number of pages9
JournalNature Microbiology
Issue number4
Early online date28 Jan 2019
Publication statusPublished - 1 Apr 2019


  • Influenza virus entry
  • Cell biology
  • Structural biology
  • Traffic


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