Ebola Virus Shed Glycoprotein Triggers Differentiation, Infection, and Death of Monocytes Through Toll-Like Receptor 4 Activation

J Infect Dis. 2018 Nov 22;218(suppl_5):S327-S334. doi: 10.1093/infdis/jiy406.

Abstract

A better understanding of the mechanisms used by Ebola virus to disable the host immune system and spread the infection are of great importance for development of new therapeutic strategies. We demonstrate that treatment of monocytic cells with Ebola virus shed glycoprotein (GP) promotes their differentiation resulting in increased infection and cell death. The effects were inhibited by blocking Toll-like receptor 4 pathway. In addition, high levels of shed GP were detected in supernatants of cells treated with Ebola vaccines. This study highlights the role of shed GP in Ebola pathogenesis and also in adverse effects associated with Ebola vaccines.

Publication types

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

MeSH terms

  • Cell Death / immunology
  • Cell Death / physiology*
  • Cell Differentiation / immunology
  • Cell Differentiation / physiology*
  • Ebola Vaccines / immunology
  • Ebolavirus / immunology
  • Ebolavirus / metabolism*
  • Glycoproteins / immunology
  • Glycoproteins / metabolism*
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / metabolism
  • Hemorrhagic Fever, Ebola / virology
  • Host-Pathogen Interactions / immunology
  • Host-Pathogen Interactions / physiology
  • Humans
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Monocytes / physiology
  • Monocytes / virology
  • THP-1 Cells / metabolism
  • THP-1 Cells / physiology
  • THP-1 Cells / virology
  • Toll-Like Receptor 4 / metabolism*
  • Viral Envelope Proteins / metabolism

Substances

  • Ebola Vaccines
  • Glycoproteins
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Viral Envelope Proteins