The role of Ran-binding protein 3 during influenza A virus replication

J Gen Virol. 2013 May;94(Pt 5):977-984. doi: 10.1099/vir.0.049395-0. Epub 2013 Jan 9.

Abstract

Influenza A virus vRNP nuclear export is CRM1-dependent. Ran-binding protein 3 (RanBP3) is a Ran-interacting protein that is best known for its role as a cofactor of CRM1-mediated cargo nuclear export. In this study, we investigated the role of RanBP3 during the influenza A virus life cycle. We found that RanBP3 was phosphorylated at Ser58 in the early and late phases of infection. Knockdown of RanBP3 expression led to vRNP nuclear retention, suggesting that RanBP3 is involved in vRNP nuclear export. Moreover, we demonstrated that the function of RanBP3 during vRNP nuclear export is regulated by phosphorylation at Ser58, and that RanBP3 phosphorylation is modulated by both PI3K/Akt and Ras/ERK/RSK pathways in the late phase of viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Butadienes / pharmacology
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Chick Embryo
  • Chromones / pharmacology
  • Dogs
  • Enzyme Inhibitors / pharmacology
  • Exportin 1 Protein
  • Gene Expression Regulation, Viral
  • Gene Knockdown Techniques
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / metabolism
  • Influenza A virus / physiology*
  • Influenza, Human / virology*
  • Karyopherins / metabolism
  • Morpholines / pharmacology
  • Nitriles / pharmacology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Serine / metabolism
  • Viral Proteins / metabolism*
  • Virus Replication / physiology*
  • ras Proteins / antagonists & inhibitors

Substances

  • Butadienes
  • Chromones
  • Enzyme Inhibitors
  • Karyopherins
  • Morpholines
  • Nitriles
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • RANBP3 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • U 0126
  • Viral Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Serine
  • ras Proteins