Phosphatase PP2CB inhibits innate immune response triggered by RNA virus VSV or SeV / 中国免疫学杂志

ABSTRACT

Objective:To investigate the role of phosphatase PP2CB in the innate immunity against RNA virus and the underlying mechanism.Methods:PP2CB expression in macrophages was silenced with the specific siRNA.The mRNA and protein expression level of type Ⅰ interferon was detected by Q-PCR and ELISA respectively.The phosphorylation level of TBK1 and IRF3 was analyzed by Western blot.Results:RNA virus VSV infection led to the expression change of PP2CB.Overexpression of PP2CB dose-dependently inhibited the activation of IFN-β reporter gene.PP2CB silencing by PP2CB siRNA significantly promoted the production of type Ⅰ interferon triggered by RNA virus VSV or SeV,and inhibited the replication of VSV in macrophages.Furthermore,PP2CB bound TBK1 upon RNA virus infection.PP2CB silencing up-regulated the phosphorylation level of TBK1 and IRF3.Conclusion:Upon RNA virus VSV or SeV infection,phosphatase PP2CB binds TBK1 and inhibits its phosphorylation to negatively regulate the activation of the antiviral innate immune signal pathway,which consequently suppresses the production of type Ⅰ interferon triggered by RNA virus VSV or SeV.