Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency

Verity G Kew; Jinxiang Yuan; Jeffery Meier; Matthew B Reeves

doi:10.1371/journal.ppat.1004195

Back

Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency

Journal article

Open access

Peer reviewed

Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency

Verity G Kew, Jinxiang Yuan, Jeffery Meier and Matthew B Reeves

PLoS pathogens, Vol.10(6), pp.e1004195-e1004195

06/2014

DOI: 10.1371/journal.ppat.1004195

PMCID: PMC4055774

PMID: 24945302

Files and links (1)

url

https://doi.org/10.1371/journal.ppat.1004195View

Published (Version of record) Open Access

Abstract

The devastating clinical consequences associated with human cytomegalovirus (HCMV) infection and reactivation underscores the importance of understanding triggers of HCMV reactivation in dendritic cells (DC). Here we show that ERK-mediated reactivation is dependent on the mitogen and stress activated kinase (MSK) family. Furthermore, this MSK mediated response is dependent on CREB binding to the viral major immediate early promoter (MIEP). Specifically, CREB binding to the MIEP provides the target for MSK recruitment. Importantly, MSK mediated phosphorylation of histone H3 is required to promote histone de-methylation and the subsequent exit of HCMV from latency. Taken together, these data suggest that CREB binding to the MIEP is necessary for the recruitment of the kinase activity of MSKs to initiate the chromatin remodelling at the MIEP required for reactivation. Thus the importance of CREB during HCMV reactivation is to promote chromatin modifications conducive for viral gene expression as well as acting as a classical transcription factor. Clearly, specific inhibition of this interaction between CREB and MSKs could provide a strategy for therapeutic intervention.

Cytomegalovirus - genetics

Okadaic Acid - pharmacology

Phosphorylation

Virus Activation - physiology

Humans

Immediate-Early Proteins - biosynthesis

Cells, Cultured

Antigens, Viral - genetics

MAP Kinase Kinase 1 - metabolism

Gene Expression Regulation, Viral - genetics

Promoter Regions, Genetic - genetics

MAP Kinase Signaling System

DNA-Binding Proteins - metabolism

Immediate-Early Proteins - genetics

Cyclic AMP Response Element-Binding Protein - metabolism

Trans-Activators - genetics

Protein Binding

Cytomegalovirus Infections - pathology

Trans-Activators - biosynthesis

Histones - metabolism

Dendritic Cells - virology

Antigens, Viral - biosynthesis

Binding Sites

Virus Latency - genetics

Details

Title: Subtitle: Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency
Creators: Verity G Kew - Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Jinxiang Yuan - Department of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Jeffery Meier - Department of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Matthew B Reeves - Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Institute of Immunity & Transplantation, Division of Infection & Immunity, Royal Free Hospital, University College London, London, United Kingdom
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.10(6), pp.e1004195-e1004195
DOI: 10.1371/journal.ppat.1004195
PMID: 24945302
PMCID: PMC4055774
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: Public Library of Science
Grant note: 0900466 / Medical Research Council G0900466 / Medical Research Council
Language: English
Date published: 06/2014
Academic Unit: Infectious Diseases; Epidemiology; Internal Medicine
Record Identifier: 9984094325402771

Metrics

19 Record Views

58 Times Cited - Web of Science

See more details