YB-1 functions as a porter to lead influenza virus ribonucleoprotein complexes to microtubules

J Virol. 2012 Oct;86(20):11086-95. doi: 10.1128/JVI.00453-12. Epub 2012 Aug 1.

Abstract

De novo-synthesized RNAs are under the regulation of multiple posttranscriptional processes by a variety of RNA-binding proteins. The influenza virus genome consists of single-stranded RNAs and exists as viral ribonucleoprotein (vRNP) complexes. After the replication of vRNP in the nucleus, it is exported to the cytoplasm and then reaches the budding site beneath the cell surface in a process mediated by Rab11a-positive recycling endosomes along microtubules. However, the regulatory mechanisms of the postreplicational processes of vRNP are largely unknown. Here we identified, as a novel vRNP-interacting protein, Y-box-binding protein 1 (YB-1), a cellular protein that is involved in regulation of cellular transcription and translation. YB-1 translocated to the nucleus from the cytoplasm and accumulated in PML nuclear bodies in response to influenza virus infection. vRNP assembled into the exporting complexes with YB-1 at PML nuclear bodies. After nuclear export, using YB-1 knockdown cells and in vitro reconstituted systems, YB-1 was shown to be required for the interaction of vRNP exported from the nucleus with microtubules around the microtubule-organizing center (MTOC), where Rab11a-positive recycling endosomes were located. Further, we also found that YB-1 overexpression stimulates the production of progeny virions in an Rab11a-dependent manner. Taking these findings together, we propose that YB-1 is a porter that leads vRNP to microtubules from the nucleus and puts it into the vesicular trafficking system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Cytoplasm / metabolism
  • Cytoplasm / virology
  • Dogs
  • Endosomes / metabolism
  • Endosomes / virology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Influenza A virus / metabolism*
  • Microtubule-Organizing Center / virology
  • Microtubules / metabolism*
  • Microtubules / virology
  • Protein Transport
  • RNA Interference
  • RNA, Small Interfering
  • Ribonucleoproteins / metabolism*
  • Viral Proteins / metabolism*
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • RNA, Small Interfering
  • Ribonucleoproteins
  • Viral Proteins
  • Y-Box-Binding Protein 1
  • rab11 protein
  • rab GTP-Binding Proteins