The Ebola-Glycoprotein modulates the function of Natural killer cells

Avishay Edri, Avishai Shemesh, Muhammed Iraqi, Omri Matalon, Michael Brusilovsky, Uzi Hadad, Olga Radinsky, Orly Gershoni-Yahalom, John M. Dye, Ofer Mandelboim, Mira Barda-Saad, Leslie Lobel, Angel Porgador

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The Ebola virus (EBOV) uses evasion mechanisms that directly interfere with host T-cell antiviral responses. By steric shielding of human leukocyte antigen class-1, the Ebola glycoprotein (GP) blocks interaction with T-cell receptors (TCRs), thus rendering T cells unable to attack virus-infected cells. It is likely that this mechanism could promote increased natural killer (NK) cell activity against GP-expressing cells by preventing the engagement of NK inhibitory receptors; however, we found that primary human NK cells were less reactive to GP-expressing HEK293T cells. This was manifested as reduced cytokine secretion, a reduction in NK degranulation, and decreased lysis of GP-expressing target cells. We also demonstrated reduced recognition of GP-expressing cells by recombinant NKG2D and NKp30 receptors. In accordance, we showed a reduced monoclonal antibody-based staining of NKG2D and NKp30 ligands on GP-expressing target cells. Trypsin digestion of the membrane-associated GP led to a recovery of the recognition of membrane-associated NKG2D and NKp30 ligands. We further showed that membrane-associated GP did not shield recognition by KIR2DL receptors; in accordance, GP expression by target cells significantly perturbed signal transduction through activating, but not through inhibitory, receptors. Our results suggest a novel evasion mechanism employed by the EBOV to specifically avoid the NK cell immune response.

Original languageEnglish
Article number1428
JournalFrontiers in Immunology
Volume9
Issue numberJUL
DOIs
StatePublished - 2 Jul 2018

Bibliographical note

Publisher Copyright:
© 2018 Edri, Shemesh, Iraqi, Matalon, Brusilovsky, Hadad, Radinsky, Gershoni-Yahalom, Dye, Mandelboim, Barda-Saad, Lobel and Porgador.

Keywords

  • Ebola
  • Ebola GP
  • MICA
  • Modulation of immune system
  • NKG2D
  • Natural killer cells
  • Steric shielding
  • Viral evasion strategies

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