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  • SARS-CoV-2 Nsp5 Activates NF-kappaB Pathway by Upregulating SUMOylation of MAVS #MMPMID34858407
  • Li W; Qiao J; You Q; Zong S; Peng Q; Liu Y; Hu S; Liu W; Li S; Shu X; Sun B
  • Front Immunol 2021[]; 12 (ä): 750969 PMID34858407show ga
  • The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1beta, IL-6, TNF-alpha, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-kappaB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-kappaB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-kappaB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-kappaB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-kappaB signaling pathway.
  • |Adaptor Proteins, Signal Transducing/genetics/*metabolism[MESH]
  • |Animals[MESH]
  • |COVID-19/immunology[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus 3C Proteases/*immunology[MESH]
  • |Cytokines/*biosynthesis[MESH]
  • |Enzyme Activation/drug effects[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Immunity, Innate/immunology[MESH]
  • |Interleukin-1beta/biosynthesis[MESH]
  • |Interleukin-2/biosynthesis[MESH]
  • |Interleukin-6/biosynthesis[MESH]
  • |NF-kappa B/*metabolism[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Signal Transduction/physiology[MESH]
  • |Sumoylation/drug effects/*physiology[MESH]
  • |THP-1 Cells[MESH]
  • |Tumor Necrosis Factor-alpha/biosynthesis[MESH]
  • |Vero Cells[MESH]

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  • suck abstract from ncbi

    750969 ä.12 2021