Transcriptional activation of the promoter of human cytomegalovirus immediate early gene (CMV-IE) by the hepatitis B viral X protein (HBx) through the NF-κB site

Abstract

The reactivation of latent cytomegalovirus (CMV) in a human by another viral infection may induce virus-related symptoms. Based on this presumption, we investigated the effect of HBx on the activation of the CMV-IE, which is also known as a transactivator and potential oncogene. The HBx transactivated the CMV-IE promoter by up to 4- and 18-fold factors in human liver HepG2 and lung fibroblast MRC-5 cells, respectively. Cotransfection of HBx with each transcription factor presented in the CMV-IE promoter showed that only NF-κB synergistically activated the promoter by up to a 14-fold factor. Serial deletion assays and point mutation analysis showed that the third NF-κB site (nt −267 to −258) and the second one (nt −162 to −153) appeared as the major responsible site and minor one, respectively, for the transactivation. These results suggest the possibility that the HBV infection of a cell previously infected by CMV would exert influence on the reactivation of the latent cytomegalovirus in a human to induce virus-related symptoms.