Co-immunoprecipitation experiments showed interactions between SARS-CoV-2 N and human MAVS upon co-expression of tagged proteins in human embryonic kidney 293T cells (HEK293T cells). Endogenous MAVS immunoprecipitated together with N in human epithelial Caco-2 cells infected with SARS-CoV-2. Overexpression of N negatively regulated activation of TBK1 and IRF3 and suppressed interactions of endogenous MAVS with endogenous TRIM31 and DDX58 (RIG-I) in Sendai virus (SeV)-stimulated HEK293T and human lung carcinoma A549 cells. In addition, tandem ubiquitin-binding entities (TUBE)-based pull-down method showed that expression of N strongly inhibited K63-linked polyubiquitination of MAVS in SeV-stimulated HEK293T and A549 cells. MAVS aggregation was also impaired by viral N. Further, acetylation by host CREB-binding protein (CREBBP, CBP) at Lys375 of viral N abrogates its LLPS and the N-mediated suppression of MAVS signaling (Wang S et al. 2021). Overall, the data suggest that SARS-CoV-2 N:RNA LLPS inhibits MAVS-mediated production of type I and III IFNs by preventing the formation of the MAVS signalosome complex.
Zhou, F, Lou, L, Dai, T, Yang, B, Zhang, L, Wang, S, Huang, H, Chu, F, Qin, Z, Lu, H, Pan, T
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