TY  - JOUR
AU  - Jarahian, Mostafa
AU  - Marstaller, Katharina
AU  - Banna, Nadine
AU  - Ahani, Roshanak
AU  - Etemadzadeh, Mohammad Hossein
AU  - Boller, Lea K
AU  - Azadmanesh, Kayhan
AU  - Cid-Arregui, Angel
AU  - Khezri, Abdolrahman
AU  - Berger, Martin R
AU  - Momburg, Frank
AU  - Watzl, Carsten
TI  - Activating Natural Killer Cell Receptors, Selectins, and Inhibitory Siglecs Recognize Ebolavirus Glycoprotein.
JO  - Journal of innate immunity
VL  - 14
IS  - 2
SN  - 1662-8128
CY  - Sydney
PB  - Karger
M1  - DKFZ-2021-01907
SP  - 135-147
PY  - 2022
N1  - #EA:G401# / 2022;14(2):135-147
AB  - 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.
KW  - Ebolavirus glycoprotein (Other)
KW  - HPV (Other)
KW  - Natural cytotoxicity receptors (Other)
KW  - Selectins (Other)
KW  - Siglecs (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34425576
DO  - DOI:10.1159/000517628
UR  - https://inrepo02.dkfz.de/record/170400
ER  -