Title |
The Ebola-Glycoprotein Modulates the Function of Natural Killer Cells
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Published in |
Frontiers in immunology, July 2018
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DOI | 10.3389/fimmu.2018.01428 |
Pubmed ID | |
Authors |
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 |
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. |
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Geographical breakdown
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Sweden | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
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Demographic breakdown
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Student > Ph. D. Student | 6 | 19% |
Student > Bachelor | 5 | 16% |
Student > Master | 3 | 10% |
Other | 2 | 6% |
Professor | 2 | 6% |
Other | 3 | 10% |
Unknown | 10 | 32% |
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Medicine and Dentistry | 3 | 10% |
Agricultural and Biological Sciences | 3 | 10% |
Nursing and Health Professions | 1 | 3% |
Other | 2 | 6% |
Unknown | 9 | 29% |