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bioRxiv · 10.1101/2023.02.24.529952

Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy

Lopez-Munoz, A. D.·Santos, J. J. S.·Yewdell, J. W.
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Abstract

We recently reported that SARS-CoV-2 Nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the seasonal human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and non-infected cells by binding heparan-sulfate/heparin (HS/H). HCoV-OC43 N binds with high affinity to the same set of 11 human CHKs as SARS-CoV-2 N, but also to a non-overlapping set of 6 cytokines (CKs). As with SARS-CoV-2 N, HCoV-OC43 N inhibits CXCL12{beta}-mediated leukocyte migration in chemotaxis assays, as do all highly pathogenic and endemic HCoV N proteins. Together, our findings indicate that cell surface HCoV N plays important evolutionary conserved roles in manipulating host innate immunity and as a target for adaptive immunity.

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Lopez-Munoz, A. D., Santos, J. J. S., Yewdell, J. W.. 2023-02-27. Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy. https://doi.org/10.1101/2023.02.24.529952

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