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Journal of Virology, April 2007, p. 3649-3651, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02079-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

AMPK-Mediated Inhibition of mTOR Kinase Is Circumvented during Immediate-Early Times of Human Cytomegalovirus Infection

Sagar B. Kudchodkar, Gregory Q. Del Prete, Tobi G. Maguire, and James C. Alwine^*

Department of Cancer Biology, Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6142

Received 22 September 2006/ Accepted 28 December 2006

Human cytomegalovirus (HCMV) infection increases synthetic rates in infected cells. The resulting increase in energy utilization could potentially increase the AMP:ATP ratio, causing activation of 5'-AMP-activated protein kinase (AMPK). Activated AMPK promotes inhibition of mammalian target of rapamycin (mTOR) kinase, which could be deleterious to the viral infection. Using the AMPK-activating drug 5-amino-4-imidazolecarboxamide ribose (AICAR), we showed that, by 12 h post-HCMV infection, inhibition of mTOR by AMPK is circumvented. However, growth curves showed that progeny virion production is inhibited when AICAR is added, suggesting other inhibitory effects of AICAR or activated AMPK.

Published ahead of print on 10 January 2007.

These authors contributed equally to this work.

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