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Induction of the unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum (ER) stress that allows a cell to reestabilish ER homeostasis.Phosphorylation of cIF2a and protein synthesis shut down is one of the UPR to reduce the protein load in ER.A diversity of strategies is evolved by RNA viruses to manipulate the host translation machinery.In cells infected with coronavirus infectious bronchitis virus (IBV),we found that de novo protein synthesis was maintained in normal level and no translational inhibition was observed.Westem blot showed that eIF2a was phosphoryfated at early infection stage,and was then dephosphorylated at late infection stage.The dephosphorylation of eIF2a contributes to the recovery of protein synthesis.One of the kinases responsible for eIF2a phosphorylation,PKR,was then examined.The results showed that the level of phosphorylated PKR was greatly reduced in IBV-infected cells.Furthermore,GADD34.a component of the protein phosphatase I (PPI) complex,which dephosphorylates eIF2a,was significantly induced in IBV-infected cells.Inhibition of the PPI activty by okadaic acid and overexpression of GADD34,eIF2a,and PKR,as well as their mutant constructs in virus-infected cells,showed that these viral regulatory strategies played a synergistic role in maintaining protein synthesis and blocking PKR activation and inducing GADD34 expression,to maintain de novo protein synthesis in IBV-infected cells and to enhance viral replication.