| First Author | Hao D | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 9 | Pages | 12392-12405 |
| PubMed ID | 32779804 | Mgi Jnum | J:307301 |
| Mgi Id | MGI:6720065 | Doi | 10.1096/fj.202000600RR |
| Citation | Hao D, et al. (2020) SHP-1 suppresses the antiviral innate immune response by targeting TRAF3. FASEB J 34(9):12392-12405 |
| abstractText | 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-kappaB 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 CK1epsilon 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. |
