Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery

Biochem Biophys Res Commun. 2016 Oct 21;479(3):429-433. doi: 10.1016/j.bbrc.2016.09.043. Epub 2016 Sep 10.

Abstract

Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion.

Keywords: Exportin; Importin; Nipah virus; Nuclear transport; Paramyxovirus; W protein.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Cytoplasm / metabolism
  • Exportin 1 Protein
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Karyopherins / metabolism*
  • Leucine / chemistry
  • Nipah Virus*
  • Nuclear Localization Signals / metabolism
  • Phosphorylation
  • Protein Domains
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction
  • Vero Cells
  • Viral Proteins / metabolism*

Substances

  • Karyopherins
  • Nuclear Localization Signals
  • Receptors, Cytoplasmic and Nuclear
  • Viral Proteins
  • W protein, Nipah virus
  • Green Fluorescent Proteins
  • Leucine