SHP‐1 suppresses the antiviral innate immune response by targeting TRAF3

作者：Doudou Hao, Yu Wang, Liuyan Li, Qian Gui, Jing Liu, Manman Li, Yihua Zhang, Ruixue Zhou, Dapeng Yan · 发表于：The FASEB Journal · 年份：2020 · DOI：10.1096/fj.202000600rr · 被引用次数：15 · 研究领域：interferon and immune responses、RNA regulation and disease、Immune Response and Inflammation

Type I interferons play a pivotal role in innate immune response to virus infection. The protein tyrosine phosphatase SHP-1 was reported to function as a negative regulator of inflammatory cytokine production by inhibiting activation of NF-κB and MAPKs during bacterial infection, however, the role of SHP-1 in regulating type I interferons remains unknown. Here, we demonstrated that knockout or knockdown of SHP-1 in macrophages promoted both HSV-1- and VSV-induced antiviral immune response. Conversely, overexpression of SHP-1 in L929 cells suppressed the HSV-1- and VSV-induced immune response; suppression was directly dependent on phosphatase activity. We identified a direct interaction between SHP-1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63-linked ubiquitination; SHP-1 inhibited K63-linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446. Taken together, our results identify SHP-1 as a negative regulator of antiviral immunity and suggest that SHP-1 may be a target for intervention in acute virus infection.