Influenza A virus uses the aggresome processing machinery for host cell entry

Indranil Banerjee, Yasuyuki Miyake, Samuel Philip Nobs, Christoph Schneider, Peter Horvath, Manfred Kopf, Patrick Matthias, Ari Helenius, Yohei Yamauchi

Research output: Contribution to journalArticle (Academic Journal)

117 Citations (Scopus)

Abstract

During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell's aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)-dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule- and actin-associated motors are essential for IAV entry.

Original languageEnglish
Pages (from-to)473-477
Number of pages5
JournalScience
Volume346
Issue number6208
DOIs
Publication statusPublished - 24 Oct 2014

Keywords

  • Animals
  • Capsid
  • Cell Line, Tumor
  • Cell Nucleus
  • Dyneins
  • Gene Knockout Techniques
  • Histone Deacetylases
  • Host-Pathogen Interactions
  • Humans
  • Influenza A virus
  • Influenza, Human
  • Membrane Fusion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins
  • Microtubules
  • Myosin Type II
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • RNA Interference
  • Ribonucleoproteins
  • Ubiquitin
  • Virus Internalization
  • Virus Replication
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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