TY - JOUR
T1 - Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection
AU - Terry, Laura J.
AU - Vastag, Livia
AU - Rabinowitz, Joshua D.
AU - Shenk, Thomas Eugene
PY - 2012/2/21
Y1 - 2012/2/21
N2 - 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.
AB - 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.
KW - Herpesvirus
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=84857428182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857428182&partnerID=8YFLogxK
U2 - 10.1073/pnas.1200494109
DO - 10.1073/pnas.1200494109
M3 - Article
C2 - 22315427
AN - SCOPUS:84857428182
SN - 0027-8424
VL - 109
SP - 3071
EP - 3076
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -