TY - JOUR
T1 - The Ebola-Glycoprotein modulates the function of Natural killer cells
AU - Edri, Avishay
AU - Shemesh, Avishai
AU - Iraqi, Muhammed
AU - Matalon, Omri
AU - Brusilovsky, Michael
AU - Hadad, Uzi
AU - Radinsky, Olga
AU - Gershoni-Yahalom, Orly
AU - Dye, John M.
AU - Mandelboim, Ofer
AU - Barda-Saad, Mira
AU - Lobel, Leslie
AU - Porgador, Angel
N1 - Publisher Copyright:
© 2018 Edri, Shemesh, Iraqi, Matalon, Brusilovsky, Hadad, Radinsky, Gershoni-Yahalom, Dye, Mandelboim, Barda-Saad, Lobel and Porgador.
PY - 2018/7/2
Y1 - 2018/7/2
N2 - 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.
AB - 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.
KW - Ebola
KW - Ebola GP
KW - MICA
KW - Modulation of immune system
KW - NKG2D
KW - Natural killer cells
KW - Steric shielding
KW - Viral evasion strategies
UR - http://www.scopus.com/inward/record.url?scp=85049402727&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.01428
DO - 10.3389/fimmu.2018.01428
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AN - SCOPUS:85049402727
SN - 1664-3224
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - JUL
M1 - 1428
ER -