AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early times of human cytomegalovirus infection.
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.
Kudchodkar
Sagar B
SB
Department of Cancer Biology, Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104-6142, USA.
Del Prete
Gregory Q
GQ
Maguire
Tobi G
TG
Alwine
James C
JC
D055372:AMP-Activated Protein Kinases; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D006801:Humans; D050296:Microbial Viability; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
D009097:Multienzyme Complexes; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases