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Journal of General Virology, Vol 80, 961-969, Copyright © 1999 by Society for General Microbiology

ARTICLES

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s)

S Kim, SS Yu, IS Lee, S Ohno, J Yim, S Kim and HS Kang
Department of Microbiology, College of Natural Sciences, Seoul National University, Korea.

During human cytomegalovirus (HCMV) infection, a rapid increase in AP-1 activity is detected. In this study, activation of transcription from promoters containing AP-1-binding sites by the IE1 protein of HCMV was examined. In transient transfection assays with reporter plasmids, it was found that IE1 strongly induced AP-1-driven transcription. Cells stably expressing IE1 also showed higher levels of AP-1 activity than did control cells. IE1 expression did not raise levels of c-jun and c- fos RNA, as determined by quantitative RT-PCR. AP-1 induction by IE1 was blocked efficiently by protein kinase inhibitors in a cell type- dependent manner; for example, by staurosporine in the human microglial cell line U373MG and by H7 in the human promonocytic cell line U937. IE1-driven activation of AP-1 was increased dramatically by mitogen- activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). The results of this study indicate that IE1 activates AP-1 at the post-transcriptional level and that MEKK1 may play an important role in this process.


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