Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and has infected more than 250 million people. A typical feature of COVID-19 is the lack of type I interferon (IFN-I)-mediated antiviral immunity in patients. However, the detailed molecular mechanisms by which SARS-CoV-2 evades the IFN-I-mediated antiviral response remain elusive. Here, we performed a comprehensive screening and identified a set of SARS-CoV-2 proteins that antagonize the IFN-I response. Subsequently, we characterized the mechanisms of two viral proteins antagonize IFN-I production and downstream signaling. SARS-CoV-2 membrane protein binds to importin karyopherin subunit alpha-6 (KPNA6) to inhibit interferon regulatory factor 3(IRF3) nuclear translocation. Further, the spike protein interacts with signal transducer and activator of transcription 1 (STAT1) to block its association with Janus kinase 1 (JAK1). This study increases our understanding of SARS-CoV-2 pathogenesis and suggests novel therapeutic targets for the treatment of COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, IFN-I, evasion, signaling pathway, antiviral immunity, 【초록키워드】 Treatment, Coronavirus disease 2019, coronavirus, Transcription, molecular mechanism, type I interferon, Spread, membrane protein, Stat1, SARS-CoV-2 pathogenesis, patients, mechanism, association, Signaling, antiviral response, therapeutic target, acute respiratory syndrome, Viral protein, Janus kinase 1, subunit, interferon regulatory factor, nuclear translocation, JAK1, IFN-I response, SARS-CoV-2 protein, downstream, bind, performed, lack, caused, inhibit, characterized, increase, the spike protein, interact, evade, KPNA6, 【제목키워드】 spike, coronavirus 2, response, respiratory, Type,