Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication

Renfeng Li, Jian Zhu, Zhi Xie, Gangling Liao, Jianyong Liu, Mei Ru Chen, Shaohui Hu, Crystal Woodard, Jimmy Lin, Sean Dixon Taverna, Prashant Desai, Richard F Ambinder, Gary Selwyn Hayward, Jiang Qian, Heng Zhu, S. Diane Hayward

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)390-400
Number of pages11
JournalCell Host and Microbe
Volume10
Issue number4
DOIs
StatePublished - Oct 4 2011

Fingerprint

Histone Acetyltransferases
Herpesviridae
Virus Replication
DNA Damage
Phosphotransferases
Human Herpesvirus 4
Human Herpesvirus 8
Protein Array Analysis
Viral Genes
Protein-Serine-Threonine Kinases
Simplexvirus
Cytomegalovirus
Antiviral Agents
Gene Expression
Infection
Proteins

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication. / Li, Renfeng; Zhu, Jian; Xie, Zhi; Liao, Gangling; Liu, Jianyong; Chen, Mei Ru; Hu, Shaohui; Woodard, Crystal; Lin, Jimmy; Taverna, Sean Dixon; Desai, Prashant; Ambinder, Richard F; Hayward, Gary Selwyn; Qian, Jiang; Zhu, Heng; Hayward, S. Diane.

In: Cell Host and Microbe, Vol. 10, No. 4, 04.10.2011, p. 390-400.

Research output: Contribution to journalArticle

@article{8da36a2db9e74af7a29155b57a81b0d3,
title = "Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication",
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.",
author = "Renfeng Li and Jian Zhu and Zhi Xie and Gangling Liao and Jianyong Liu and Chen, {Mei Ru} and Shaohui Hu and Crystal Woodard and Jimmy Lin and Taverna, {Sean Dixon} and Prashant Desai and Ambinder, {Richard F} and Hayward, {Gary Selwyn} and Jiang Qian and Heng Zhu and Hayward, {S. Diane}",
year = "2011",
month = "10",
day = "4",
doi = "10.1016/j.chom.2011.08.013",
language = "English (US)",
volume = "10",
pages = "390--400",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication

AU - Li, Renfeng

AU - Zhu, Jian

AU - Xie, Zhi

AU - Liao, Gangling

AU - Liu, Jianyong

AU - Chen, Mei Ru

AU - Hu, Shaohui

AU - Woodard, Crystal

AU - Lin, Jimmy

AU - Taverna, Sean Dixon

AU - Desai, Prashant

AU - Ambinder, Richard F

AU - Hayward, Gary Selwyn

AU - Qian, Jiang

AU - Zhu, Heng

AU - Hayward, S. Diane

PY - 2011/10/4

Y1 - 2011/10/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80054896036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054896036&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2011.08.013

DO - 10.1016/j.chom.2011.08.013

M3 - Article

C2 - 22018239

AN - SCOPUS:80054896036

VL - 10

SP - 390

EP - 400

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 4

ER -