Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poliovirus-encoded protease 3Cpro

Abstract

Host cell RNA polymerase II-mediated transcription is inhibited by poliovirus infection. Previous studies from our laboratory showed that activated transcription from a cyclic AMP-responsive element (CRE)-containing promoter was severely inhibited in extracts prepared from poliovirus-infected HeLa cells compared to those from mock-infected cells. Here we demonstrate that the CRE-binding protein, CREB, is specifically cleaved by the poliovirus-encoded protease 3Cpro both in vitro and in virus-infected cells. The proteolytic cleavage of CREB leads to a significant loss of its DNA binding as well as transcriptional activity. Additionally, we demonstrate that the phosphorylated, transcriptionally active form of CREB is cleaved by the viral protease in vitro. The results presented here suggest that a direct cleavage of CREB by the viral protease 3Cpro leads to inhibition of CREB-activated transcription in poliovirus-infected HeLa cells.