SHP-1 suppresses the antiviral innate immune response by targeting TRAF3.
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-?B 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 CK1? 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.
Mesh Terms:
Animals, HEK293 Cells, Humans, Immunity, Innate, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6, RAW 264.7 Cells, TNF Receptor-Associated Factor 3, Ubiquitination, Virus Diseases
Animals, HEK293 Cells, Humans, Immunity, Innate, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6, RAW 264.7 Cells, TNF Receptor-Associated Factor 3, Ubiquitination, Virus Diseases
FASEB J
Date: Dec. 01, 2019
PubMed ID: 32779804
View in: Pubmed Google Scholar
Download Curated Data For This Publication
229167
Switch View:
- Interactions 8