Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells

Nat Commun. 2015 Feb 11;6:6240. doi: 10.1038/ncomms7240.

Abstract

Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB(23-431). Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma
  • Cell Line, Tumor
  • Endocytosis
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Epstein-Barr Virus Infections / metabolism*
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology
  • ErbB Receptors / metabolism
  • Glycoproteins / metabolism
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Membrane Fusion
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology*
  • Neuropilin-1 / metabolism*
  • Neuropilin-2 / metabolism
  • Protein Binding
  • Protein Transport
  • Signal Transduction
  • Virus Internalization*

Substances

  • Glycoproteins
  • Neuropilin-2
  • Neuropilin-1
  • ErbB Receptors