摘要
The ongoing 2019 novel coronavirus disease(COVID-19)caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat.The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms.However,the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown.Here,we demonstrate that SARS-CoV-2 nucleocapsid(N)protein,the major structural protein of the virion,promotes the virus-triggered activation of NF-kB signaling.After binding to viral RNA,N protein robustly undergoes liquid-liquid phase separation(LLPS),which recruits TAK1 and IKK complex,the key kinases of NF-kB signaling,to enhance NF-kB activation.Moreover,1,6-hexanediol,the inhibitor of LLPS,can attenuate the phase separation of N protein and restrict its regulatory functions in NF-kB activation.These results suggest that LLPS of N protein provides a platform to Induce NF-kB hyper-activation,which could be a potential therapeutic target against COVID-19 severe pneumonia.
基金
This work was supported by the National Key R&D Program of China(2020YFA0908700 and 2020YFC0842400)
National Natural Science Foundation of China(31870862,82025001,31700760,31970700,and 31800751)
Guangdong Basic and Applied Basic Research Foundation(2020B1515120090)
the Fundamental Research Funds for the Central Universities(18lgpy49 and 18lgpy53)
Natural Science Foundation of Guangdong Province,China(2021A1515012179).