摘要
The recently emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is the causative agent of ongoing global pan demic of COVID-19,may trigger imm uno suppression in the early stage and overactive immune resp onse in the late stage of infection;However,the un derlying mecha nisms are not well understood.Here we dem on strated 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 dually regulated the phosphorylation and nuclear translocation of IRF3,STAT1,and STAT2.Additi on ally,low-dose N protein combined with TRIM25 could suppress the ubiquitination and activatio n of retinoic acidinducible gene I(RIG-I).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.
基金
supported by grant from National Natural Science Foundation of China(81972873,81871699,82072330)
the Pearl River Talent Plan in Guangdong Province of China(2019CX01N111)
the Science and Technology Innovation Project in Foshan and Guangzhou,Guangdong Province,China(2020001000151,202103000008)
the Foundation of Jilin Province Science and Technology Department(172408GHO10234983 and 20200301001RQ)
the 68th batch of first-class funding from China Postdoctoral Science Foundation(2020M680044).
