Cell-cell contact promotes Ebola virus GP-mediated infection

Virology. 2016 Jan 15:488:202-15. doi: 10.1016/j.virol.2015.11.019. Epub 2015 Dec 3.

Abstract

Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Here we provide evidence that cell-cell contact promotes infection mediated by the glycoprotein (GP) of EBOV. Interestingly, expression of EBOV GP alone, even in the absence of retroviral Gag-Pol, is sufficient to transfer a retroviral vector encoding Tet-off from cell to cell. Cell-to-cell infection mediated by EBOV GP is blocked by inhibitors of actin polymerization, but appears to be less sensitive to KZ52 neutralization. Treatment of co-cultured cells with cathepsin B/L inhibitors, or an entry inhibitor 3.47 that targets the receptor NPC1 for virus binding, also blocks cell-to-cell infection. Cell-cell contact also enhances spread of rVSV bearing GP in monocytes and macrophages, the primary targets of natural EBOV infection. Altogether, our study reveals that cell-cell contact promotes EBOV GP-mediated infection, and provides new insight into understanding EBOV spread and viral pathogenesis.

Keywords: Cell-to-cell infection; Ebola virus; GP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / metabolism
  • Cell Line
  • Ebolavirus / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / metabolism
  • Niemann-Pick C1 Protein
  • Receptors, Virus / metabolism
  • Viral Envelope Proteins / metabolism*
  • Virus Internalization*

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein
  • Receptors, Virus
  • Viral Envelope Proteins
  • envelope glycoprotein, Ebola virus