| Autor: |
Kocsis A; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary., Bartus D; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary., Hirsch E; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Hungary., Józsi M; Department of Immunology, ELTE Eötvös Loránd University, H-1117 Budapest, Hungary.; HUN-REN-ELTE Complement Research Group, Hungarian Research Network, H-1117 Budapest, Hungary., Hajdú I; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary., Dobó J; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary., Balczer J; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary., Pál G; Department of Biochemistry, ELTE Eötvös Loránd University, H-1117 Budapest, Hungary., Gál P; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, H-1117 Budapest, Hungary. |
| Abstrakt: |
The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral structural protein that is abundant in the circulation of infected individuals. Previous published studies reported controversial data about the role of the N protein in the activation of the complement system. It was suggested that the N protein directly interacts with mannose-binding lectin-associated serine protease-2 (MASP-2) and stimulates lectin pathway overactivation/activity. In order to check these data and to reveal the mechanism of activation, we examined the effect of the N protein on lectin pathway activation. We found that the N protein does not bind to MASP-2 and MASP-1 and it does not stimulate lectin pathway activity in normal human serum. Furthermore, the N protein does not facilitate the activation of zymogen MASP-2, which is MASP-1 dependent. Moreover, the N protein does not boost the enzymatic activity of MASP-2 either on synthetic or on protein substrates. In some of our experiments, we observed that MASP-2 digests the N protein. However, it is questionable, whether this activity is biologically relevant. Although surface-bound N protein did not activate the lectin pathway, it did trigger the alternative pathway in 10% human serum. Additionally, we detected some classical pathway activation by the N protein. Nevertheless, we demonstrated that this activation was induced by the bound nucleic acid, rather than by the N protein itself. |
