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Evolution of a truncated nucleocapsid protein enhances SARS-CoV-2 fitness by suppressing antiviral responses - PubMed

19 hours ago
  • #SARS-CoV-2 evolution
  • #Antiviral evasion
  • #Nucleocapsid protein
  • SARS-CoV-2 evolves a truncated nucleocapsid protein, N*M210, due to acquisition of a viral transcription regulatory sequence (TRS) in the N gene, particularly in variants like Omicron, leading to increased production.
  • N*M210 functions as a double-stranded RNA (dsRNA)-binding protein, inhibiting multiple antiviral responses by suppressing interferon, disassembling processing bodies, and blocking G3BP1 foci (e.g., stress granules and RNase L-dependent bodies).
  • Enhanced N*M210 production boosts SARS-CoV-2 fitness in primary human cells and mice, as demonstrated with recombinant viruses, by evading dsRNA-induced antiviral responses and tipping cellular control in favor of the virus.