SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO

SARS-CoV-2 infection elicits a dysregulation of immune response characterized by a delayed interferon expression. SARS-CoV-2 ORF9b is an accessory protein that plays an important role for the suppression of interferon responses by interfering the activation of NF-kB. NEMO (NF-kappa-B essential modulator) is a key activator of NF-kB, whose regulation requires its K63-linked polyubiquitination. ORF9b interacts with NEMO, and interrupts the polyubiquitination, leading to the suppression of interferon responses in viral infected cells.