Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection.
Human cytomegalovirus (HCMV) modulates numerous cellular signaling pathways. Alterations in signaling are evident from the broad changes in cellular phosphorylation that occur during HCMV infection and from the altered activity of multiple kinases. Here we report a comprehensive RNAi screen, which predicts that 106 cellular kinases influence growth of the virus, most of which were not previously linked to HCMV replication. Multiple elements of the AMP-activated protein kinase (AMPK) pathway scored in the screen. As a regulator of carbon and nucleotide metabolism, AMPK is poised to activate many of the metabolic pathways induced by HCMV infection. An AMPK inhibitor, compound C, blocked a substantial portion of HCMV-induced metabolic changes, inhibited the accumulation of all HCMV proteins tested, and markedly reduced the production of infectious progeny. We propose that HCMV requires AMPK or related activity for viral replication and reprogramming of cellular metabolism.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Laura J
LJ
Terry
Livia
L
Vastag
Joshua D
JD
Rabinowitz
Thomas
T
Shenk
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000201:enzymology* / Q000821:virology*; D006801:Humans; D055442:Metabolome / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases