tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2021 Apr 24;6(1):167.
doi: 10.1038/s41392-021-00575-7.
RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-?B hyper-activation and inflammation
Yaoxing Wu[SUP] #[/SUP][SUP] 1 [/SUP], Ling Ma[SUP] #[/SUP][SUP] 1 [/SUP], Sihui Cai[SUP] #[/SUP][SUP] 1 [/SUP], Zhen Zhuang[SUP] #[/SUP][SUP] 2 [/SUP], Zhiyao Zhao[SUP] 1 2 [/SUP], Shouheng Jin[SUP] 1 [/SUP], Weihong Xie[SUP] 1 [/SUP], Lingli Zhou[SUP] 1 [/SUP], Lei Zhang[SUP] 1 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Jun Cui[SUP] 4 [/SUP]
Affiliations
Abstract
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-?B 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-?B signaling, to enhance NF-?B activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-?B activation. These results suggest that LLPS of N protein provides a platform to induce NF-?B hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.
. 2021 Apr 24;6(1):167.
doi: 10.1038/s41392-021-00575-7.
RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-?B hyper-activation and inflammation
Yaoxing Wu[SUP] #[/SUP][SUP] 1 [/SUP], Ling Ma[SUP] #[/SUP][SUP] 1 [/SUP], Sihui Cai[SUP] #[/SUP][SUP] 1 [/SUP], Zhen Zhuang[SUP] #[/SUP][SUP] 2 [/SUP], Zhiyao Zhao[SUP] 1 2 [/SUP], Shouheng Jin[SUP] 1 [/SUP], Weihong Xie[SUP] 1 [/SUP], Lingli Zhou[SUP] 1 [/SUP], Lei Zhang[SUP] 1 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Jun Cui[SUP] 4 [/SUP]
Affiliations
- PMID: 33895773
- DOI: 10.1038/s41392-021-00575-7
Abstract
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-?B 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-?B signaling, to enhance NF-?B activation. Moreover, 1,6-hexanediol, the inhibitor of LLPS, can attenuate the phase separation of N protein and restrict its regulatory functions in NF-?B activation. These results suggest that LLPS of N protein provides a platform to induce NF-?B hyper-activation, which could be a potential therapeutic target against COVID-19 severe pneumonia.