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Journal of Virology, November 1998, p. 9173-9180, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Extracellular Signal-Regulated Kinase Activity Is Sustained Early during Human Cytomegalovirus Infection

Steven M. Rodemsdagger and Deborah H. Spector*

Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0357

Received 1 June 1998/Accepted 11 August 1998

Expression of many early viral genes during human cytomegalovirus (HCMV) infection is dependent on cellular transcription factors. Several immediate-early and early viral promoters contain DNA binding sites for cellular factors such as CREB, AP-1, serum response factor, and Elk-1, and these transcription factors can be activated by phosphorylation via the cellular mitogen-activated protein kinase (MAPK) signal transduction cascade. To determine if the extracellular signal-regulated MAPKs, ERK1 and ERK2, play a role in transcription factor activation during infection, we tested for ERK activity during viral infection. We found that HCMV infection resulted in the maintenance of previously activated ERK1 and ERK2 by a mechanism which appears to involve the inhibition of a cellular phosphatase activity. ERK phosphorylation and activity were sustained for at least 8 h after infection, whereas in mock-infected cells, ERK activity steadily declined by 1 h postinfection. The activity of at least one cellular substrate of the ERKs, the protein kinase RSK1, was also maintained during this period. UV inactivation experiments suggested that viral gene expression was required for sustained ERK activity. In turn, activation of the ERKs appeared to be important for viral gene expression, as evidenced by the observed decrease in the transcriptional activity of the HCMV UL112-113 promoter during infection in the presence of the MEK inhibitor PD98059. These data suggest that HCMV utilizes cellular signal transduction pathways to activate viral or cellular transcription factors involved in the control of early viral gene expression and DNA replication.

* Corresponding author. Mailing address: Department of Biology, 0357, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0357. Phone: (619) 534-9737. Fax: (619) 534-6083. E-mail: dspector{at}ucsd.edu.

dagger Present address: Aurora Biosciences Corporation, San Diego, CA 92121.

Journal of Virology, November 1998, p. 9173-9180, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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