Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its patho...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its pathogenesis and to develop antiviral therapies.Both DNA and RNA viruses can modulate cell cycle progression to maximize their replication.1 However,the effects of SARS-CoV-2 on cell cycle progression remains largely unknown.展开更多
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 i...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.展开更多
基金This work was supported by grant from the National Natural Science Foundation of China(81972873,82002165,81871699,and 82072330)the Biosafety Research Special Plan of the Logistics Support Department of the Military Commission(923070201202)+5 种基金the young and middle-aged science and technology innovation leaders and teams of the Jilin Provincial Department of Science and Technology(20200301001RQ)China Ministry of Science and Technology Key Research and Development Program(2022YFF1203204)Jilin Province Pathogen and Infection Informatics International Joint Research Center(20210504004GH)the Pearl River Talent Plan in Guangdong Province of China(2019CX01N111)the Scientific and Technological Research Projects of Guangzhou,China(202103000008)the Medical Innovation Team Project of Jilin University(2022JBGS02).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the COVID-19 pandemic,has posed severe threats to global public health,highlighting an urgent need to understand its pathogenesis and to develop antiviral therapies.Both DNA and RNA viruses can modulate cell cycle progression to maximize their replication.1 However,the effects of SARS-CoV-2 on cell cycle progression remains largely unknown.
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)+2 种基金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).
文摘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.
