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. 2007 Apr;81(7):3649-51.
doi: 10.1128/JVI.02079-06. Epub 2007 Jan 10.

AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early times of human cytomegalovirus infection

Sagar B Kudchodkar  1 , Gregory Q Del Prete, Tobi G Maguire, James C Alwine
Affiliations

AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early times of human cytomegalovirus infection

Sagar B Kudchodkar et al. J Virol. 2007 Apr.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Control of mTOR activity by the PI3K/Akt pathway and AMPK.
FIG. 2.
FIG. 2.
Western blots showing that by 12 hpi HCMV circumvents the inhibition of mTOR by AICAR-activated AMPK. See the text for details. The separated sections of each panel are from the same Western blot and the same exposure. pS6K, phosphorylated S6 kinase; pS6, phosphorylated S6 protein; Tot. S6, total level of S6; p4E BP, phosphorylated eIF4E binding protein; Tot. 4E BP, total level of 4E BP.
FIG. 3.
FIG. 3.
Western blots showing phosphorylation of AMPK induced by AICAR during HCMV infection. See the text for details. The separated sections of each panel are from the same Western blot and the same exposure. Total AMPK levels did not change significantly during HCMV infection in the absence or presence of AICAR (data not shown). pAMPK, phosphorylated AMPK; pS6K, phosphorylated S6 kinase.
FIG. 4.
FIG. 4.
HCMV growth curves showing that the addition of AICAR for a 24-h interval at any point in the infection time course causes inhibition of progeny virion formation. See the text for details. WT, wild type.
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