Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection

Laura J. Terry, Livia Vastag, Joshua D. Rabinowitz, Thomas Eugene Shenk

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3071-3076
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number8
DOIs
StatePublished - Feb 21 2012

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Herpesvirus
  • siRNA

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