The Ebola-Glycoprotein Modulates the Function of Natural Killer Cells.
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Edri A, Shemesh A, Iraqi M, Matalon O, Brusilovsky M, Hadad U, Radinsky O, Gershoni-Yahalom O, Dye JM, Mandelboim O, Barda-Saad M, Lobel L, Porgador A
The Ebola-Glycoprotein Modulates the Function of Natural Killer Cells.
Front Immunol. 2018 Jul 2;9:1428. doi: 10.3389/fimmu.2018.01428. eCollection 2018.
- PubMed ID
- 30013549 [ View in PubMed]
- 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.