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bioRxiv · 10.1101/2021.02.17.431755

SARS-CoV-2 nucleocapsid protein dually regulates innate immune responses

Zhao, Y.·Sui, L.·Wu, P.·Wang, W.·Tan, G.·Wang, Z.·Yu, Y.·Hou, Z.·Wang, G.·Liu, Q.
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Abstract

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein interacted with the tripartite motif protein 25 (TRIM25), thereby dually regulating the phosphorylation and nuclear translocation of IRF3, STAT1 and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress retinoic acid-inducible gene I (RIG-I) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

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Zhao, Y., Sui, L., Wu, P., Wang, W., Tan, G., Wang, Z., Yu, Y., Hou, Z., Wang, G., Liu, Q.. 2021-02-18. SARS-CoV-2 nucleocapsid protein dually regulates innate immune responses. https://doi.org/10.1101/2021.02.17.431755

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