USP19 suppresses cellular type I interferon signaling by targeting TRAF3 for deubiquitination

Abstract

Aim: To investigate host factors that mediate the immune escape of enterovirus 71 (EV71) in the context of deubiquitinating enzymes. Materials & methods: Utilize PCR array to screen candidate genes that may be involved in EV71-induced cellular antiviral immune responses, and utilize protein mass spectrometry analysis to identify the functional targets of the candidate regulator. Results: EV71 infection induces the upregulation of ubiquitin-specific protease 19 (USP19) gene expression, which negatively regulates cellular antiviral type I interferon signaling. Additionally, we identify that USP19 suppresses cellular type I interferon signaling by targeting tumor necrosis factor receptor-associated factor 3 (TRAF3) molecule and decreasing TRAF3 ubiquitination of K63-linkage. Conclusion: This work suggests that USP19 is a previously unrecognized regulator employed by EV71 to evade host antiviral defenses.