Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication
Journal
Cell Host and Microbe
Journal Volume
10
Journal Issue
4
Pages
390-400
Date Issued
2011
Author(s)
Li, Renfeng
Zhu, Jian
Xie, Zhi
Liao, Gangling
Liu, Jianyong
Hu, Shaohui
Woodard, Crystal
Lin, Jimmy
Taverna, Sean D.
Desai, Prashant
Ambinder, Richard F.
Hayward, Gary S.
Qian, Jiang
Zhu, Heng
Hayward, S. Diane
Abstract
Herpesviruses, which are major human pathogens, establish life-long persistent infections. Although the α, β, and γ herpesviruses infect different tissues and cause distinct diseases, they each encode a conserved serine/threonine kinase that is critical for virus replication and spread. The extent of substrate conservation and the key common cell-signaling pathways targeted by these kinases are unknown. Using a human protein microarray high-throughput approach, we identify shared substrates of the conserved kinases from herpes simplex virus, human cytomegalovirus, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus. DNA damage response (DDR) proteins were statistically enriched, and the histone acetyltransferase TIP60, an upstream regulator of the DDR pathway, was required for efficient herpesvirus replication. During EBV replication, TIP60 activation by the BGLF4 kinase triggers EBV-induced DDR and also mediates induction of viral lytic gene expression. Identification of key cellular targets of the conserved herpesvirus kinases will facilitate the development of broadly effective antiviral strategies. ? 2011 Elsevier Inc.
Other Subjects
dna damage response protein; histone acetyltransferase; phosphotransferase; protein; protein tip60; unclassified drug; virus enzyme; Alphaherpesvirinae; article; Betaherpesvirinae; Epstein Barr virus; Gammaherpesvirinae; gene expression; Herpes virus; Human cytomegalovirus; Human herpesvirus 8; nonhuman; priority journal; virus gene; virus replication; Conserved Sequence; DNA Damage; DNA Repair Enzymes; Herpesviridae; Histone Acetyltransferases; Host-Pathogen Interactions; Humans; Microarray Analysis; Models, Biological; Protein Array Analysis; Protein-Serine-Threonine Kinases; Virus Replication; Herpesviridae; Human herpesvirus 4; Human herpesvirus 5; Human herpesvirus 8; Simplexvirus
Type
journal article