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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Signal+Transduct+Target+Ther 2021 ; 6 (1): 167 Nephropedia Template TP
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RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-kappaB hyper-activation and inflammation #MMPMID33895773
Wu Y; Ma L; Cai S; Zhuang Z; Zhao Z; Jin S; Xie W; Zhou L; Zhang L; Zhao J; Cui J
Signal Transduct Target Ther 2021[Apr]; 6 (1): 167 PMID33895773show ga
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-kappaB 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-kappaB signaling, to enhance NF-kappaB activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-kappaB activation. These results suggest that LLPS of N protein provides a platform to induce NF-kappaB hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.