Activating Natural Killer Cell Receptors, Selectins, and Inhibitory Siglecs Recognize Ebolavirus Glycoprotein.

Autor: Jarahian M; Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Marstaller K; Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Banna N; Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Ahani R; Department of Virology, Pasteur Institute of Iran, Tehran, Iran., Etemadzadeh MH; Department of Virology, Pasteur Institute of Iran, Tehran, Iran., Boller LK; Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany., Azadmanesh K; Department of Virology, Pasteur Institute of Iran, Tehran, Iran., Cid-Arregui A; Targeted Tumor Vaccines Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Khezri A; Department of Biotechnology, Inland Norway University of Applied Sciences, Hamar, Norway., Berger MR; Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Momburg F; Antigen Presentation and T/NK Cell Activation Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Watzl C; Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany.
Jazyk: angličtina
Zdroj: Journal of innate immunity [J Innate Immun] 2022; Vol. 14 (2), pp. 135-147. Date of Electronic Publication: 2021 Aug 23.
DOI: 10.1159/000517628
Abstrakt: Expression of the extensively glycosylated Ebolavirus glycoprotein (EBOV-GP) induces physical alterations of surface molecules and plays a crucial role in viral pathogenicity. Here we investigate the interactions of EBOV-GP with host surface molecules using purified EBOV-GP, EBOV-GP-transfected cell lines, and EBOV-GP-pseudotyped lentiviral particles. Subsequently, we wanted to examine which receptors are involved in this recognition by binding studies to cells transfected with the EBOV-GP as well as to recombinant soluble EBOV-GP. As the viral components can also bind to inhibitory receptors of immune cells (e.g., Siglecs, TIM-1), they can even suppress the activity of immune effector cells. Our data show that natural killer (NK) cell receptors NKp44 and NKp46, selectins (CD62E/P/L), the host factors DC-SIGNR/DC-SIGN, and inhibitory Siglecs function as receptors for EBOV-GP. Our results show also moderate to strong avidity of homing receptors (P-, L-, and E-selectin) and DC-SIGNR/DC-SIGN to purified EBOV-GP, to cells transfected with EBOV-GP, as well as to the envelope of a pseudotyped lentiviral vector carrying the EBOV-GP. The concomitant activation and inhibition of the immune system exemplifies the evolutionary antagonism between the immune system and pathogens. Altogether these interactions with activating and inhibitory receptors result in a reduced NK cell-mediated lysis of EBOV-GP-expressing cells. Modulation of these interactions may provide new strategies for treating infections caused by this virus.
(© 2021 The Author(s) Published by S. Karger AG, Basel.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje