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- W2004083964 abstract "Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling.Background: The molecular mechanism of coronavirus PLPs suppressing the innate immune response remains unclear.Results: PLP2 induces the degradation of p53 through stabilizing MDM2, and IRF7 is a novel target gene of p53.Conclusion: PLP2 inhibits the p53-mediated production of type I IFN and apoptosis to ensure viral growth.Significance: We identify the mechanism with which coronavirus induces the low dosage IFN production. Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling. Background: The molecular mechanism of coronavirus PLPs suppressing the innate immune response remains unclear. Results: PLP2 induces the degradation of p53 through stabilizing MDM2, and IRF7 is a novel target gene of p53. Conclusion: PLP2 inhibits the p53-mediated production of type I IFN and apoptosis to ensure viral growth. Significance: We identify the mechanism with which coronavirus induces the low dosage IFN production." @default.
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- W2004083964 date "2015-01-01" @default.
- W2004083964 modified "2023-10-16" @default.
- W2004083964 title "p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling" @default.
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- W2004083964 doi "https://doi.org/10.1074/jbc.m114.619890" @default.
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