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

• Published in: Journal of innate immunity 2022, Vol.14 (2), p.135-147
• Main Authors: Jarahian, Mostafa, Marstaller, Katharina, Banna, Nadine, Ahani, Roshanak, Etemadzadeh, Mohammad Hossein, Boller, Lea K., Azadmanesh, Kayhan, Cid-Arregui, Angel, Khezri, Abdolrahman, Berger, Martin R., Momburg, Frank, Watzl, Carsten
• Format: Article
• Language: English
• Subjects: Ebolavirus - physiology; ebolavirus glycoprotein; Glycoproteins - metabolism; hpv; natural cytotoxicity receptors; Receptors, Natural Killer Cell - metabolism; Research Article; selectins; Selectins - metabolism; Sialic Acid Binding Immunoglobulin-like Lectins - metabolism; siglecs; Viral Envelope Proteins - metabolism
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000517628

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.