Ubiquitination of SARS-CoV-2 NSP6 and ORF7a Facilitates NF-κB Activation
Hironori Nishitsuji, Satoko Iwahori, Mariko Ohmori, Kunitada Shimotohno, Takayuki Murata
Abstract
The detailed molecular basis of the induction of proinflammatory cytokines and chemokines by SARS-CoV-2 is unclear, although such induction is clearly related to the severity of COVID-19. Here, we show that SARS-CoV-2 NSP6 and ORF7a lead to NF-κB activation through associations with TAK1. K63-linked polyubiquitination of NSP6 and ORF7a by TRIM13 and RNF121, respectively, appears essential for NF-κB activation. These results suggest that inhibition of the NSP6 and ORF7a gene products may reduce the severity of COVID-19 symptoms by decreasing proinflammatory cytokine levels.
Topics & Concepts
Proinflammatory cytokineUbiquitin ligaseUbiquitinNF-κBNFKB1Gene knockdownCell biologyIκB kinaseCytokineChemokinePathogenesisImmune systemBiologyImmunologyTranscription factorChemistrySignal transductionInflammationGeneBiochemistrySARS-CoV-2 and COVID-19 Researchinterferon and immune responsesCOVID-19 Clinical Research Studies