The DNA Architectural Protein HMGB1 Facilitates RTA-Mediated Viral Gene Expression in Gamma-2 Herpesviruses

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Published inJournal of Virology Vol. 78; no. 23; pp. 12940 - 12950
Main Authors Song, Moon Jung, Hwang, Seungmin, Wong, Wendy, Round, June, Martinez-Guzman, Deeann, Turpaz, Yaron, Liang, Jie, Wong, Ben, Johnson, Reid C, Carey, Michael, Sun, Ren
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.12.2004
Subjects
Animals
Base Sequence
Biological and medical sciences
Cell Line
Cricetinae
Fundamental and applied biological sciences. Psychology
Gammaherpesvirus
Genetics
Herpesvirus 8, Human - genetics
HMGB1 Protein - physiology
Humans
Immediate-Early Proteins - physiology
Kaposi's sarcoma-associated herpesvirus
Microbiology
Miscellaneous
Molecular Sequence Data
Murine gammaherpesvirus 68
Response Elements
Rhadinovirus - genetics
Trans-Activators - physiology
Transcriptional Activation
Viral Proteins - physiology
Virology
Virus Replication
Gene
Microbiology
Gene expression
DNA
Protein
Virology
Online AccessGet full text

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Abstract Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
AbstractList Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gamma herpesvirus 68 (MHV-68), plays a critical role in controlling the viral life cycle. RTA acts as a strong transcription activator for several downstream genes of KSHV and MHV-68 through direct DNA binding, as well as via indirect mechanisms. HMGB1 (also called HMG-1) protein is a highly conserved nonhistone chromatin protein with the ability to bind and bend DNA. HMGB1 protein promoted RTA binding to different RTA target sites in vitro, with greater enhancement to low-affinity sites than to high-affinity sites. Box A or box B and homologues of HMGB1 also enhanced RTA binding to DNA. Transient transfection of HMGB1 stimulated RTA transactivation of RTA-responsive promoters from KSHV and MHV-68. Furthermore, MHV-68 viral gene expression, as well as viral replication, was significantly reduced in HMGB1 -deficient cells than in the wild type. This abated viral gene expression was partially restored by HMGB1 transfection into HMGB1 −/− cells. These results suggest an important function of the DNA architectural protein, HMGB1, in RTA-mediated gene expression, as well as viral replication in gamma-2 herpesviruses.
ABSTRACT Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gamma herpesvirus 68 (MHV-68), plays a critical role in controlling the viral life cycle. RTA acts as a strong transcription activator for several downstream genes of KSHV and MHV-68 through direct DNA binding, as well as via indirect mechanisms. HMGB1 (also called HMG-1) protein is a highly conserved nonhistone chromatin protein with the ability to bind and bend DNA. HMGB1 protein promoted RTA binding to different RTA target sites in vitro, with greater enhancement to low-affinity sites than to high-affinity sites. Box A or box B and homologues of HMGB1 also enhanced RTA binding to DNA. Transient transfection of HMGB1 stimulated RTA transactivation of RTA-responsive promoters from KSHV and MHV-68. Furthermore, MHV-68 viral gene expression, as well as viral replication, was significantly reduced in HMGB1 -deficient cells than in the wild type. This abated viral gene expression was partially restored by HMGB1 transfection into HMGB1 −/− cells. These results suggest an important function of the DNA architectural protein, HMGB1, in RTA-mediated gene expression, as well as viral replication in gamma-2 herpesviruses.
Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gamma herpesvirus 68 (MHV-68), plays a critical role in controlling the viral life cycle. RTA acts as a strong transcription activator for several downstream genes of KSHV and MHV-68 through direct DNA binding, as well as via indirect mechanisms. HMGB1 (also called HMG-1) protein is a highly conserved nonhistone chromatin protein with the ability to bind and bend DNA. HMGB1 protein promoted RTA binding to different RTA target sites in vitro, with greater enhancement to low-affinity sites than to high-affinity sites. Box A or box B and homologues of HMGB1 also enhanced RTA binding to DNA. Transient transfection of HMGB1 stimulated RTA transactivation of RTA-responsive promoters from KSHV and MHV-68. Furthermore, MHV-68 viral gene expression, as well as viral replication, was significantly reduced in HMGB1-deficient cells than in the wild type. This abated viral gene expression was partially restored by HMGB1 transfection into HMGB1(-/-) cells. These results suggest an important function of the DNA architectural protein, HMGB1, in RTA-mediated gene expression, as well as viral replication in gamma-2 herpesviruses.
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Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gamma herpesvirus 68 (MHV-68), plays a critical role in controlling the viral life cycle. RTA acts as a strong transcription activator for several downstream genes of KSHV and MHV-68 through direct DNA binding, as well as via indirect mechanisms. HMGB1 (also called HMG-1) protein is a highly conserved nonhistone chromatin protein with the ability to bind and bend DNA. HMGB1 protein promoted RTA binding to different RTA target sites in vitro, with greater enhancement to low-affinity sites than to high-affinity sites. Box A or box B and homologues of HMGB1 also enhanced RTA binding to DNA. Transient transfection of HMGB1 stimulated RTA transactivation of RTA-responsive promoters from KSHV and MHV-68. Furthermore, MHV-68 viral gene expression, as well as viral replication, was significantly reduced in HMGB1-deficient cells than in the wild type. This abated viral gene expression was partially restored by HMGB1 transfection into HMGB1 super(-/-) cells. These results suggest an important function of the DNA architectural protein, HMGB1, in RTA-mediated gene expression, as well as viral replication in gamma-2 herpesviruses.
Author Seungmin Hwang
Wendy Wong
DeeAnn Martinez-Guzman
Ren Sun
Ben Wong
Michael Carey
Jie Liang
Moon Jung Song
June Round
Reid C. Johnson
Yaron Turpaz
AuthorAffiliation Department of Molecular and Medical Pharmacology, UCLA AIDS Institute, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, Dental Research Institute, 1 Department of Biological Chemistry, University of California at Los Angeles, Los Angeles, California, 3 Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 2
AuthorAffiliation_xml – name: Department of Molecular and Medical Pharmacology, UCLA AIDS Institute, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, Dental Research Institute, 1 Department of Biological Chemistry, University of California at Los Angeles, Los Angeles, California, 3 Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 2
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Corresponding author. Mailing address: Department of Molecular and Medical Pharmacology, Center for Health Sciences, 12-120, University of California at Los Angeles, Los Angeles, CA 90095. Phone: (310) 794-5557. Fax: (310) 825-6267. E-mail: rsun@mednet.ucla.edu.
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Snippet Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley...
Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated herpesvirus...
ABSTRACT Replication and transcription activator (RTA), an immediate-early gene product of gamma-2 herpesviruses including Kaposi's sarcoma-associated...
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StartPage 12940
SubjectTerms Animals
Base Sequence
Biological and medical sciences
Cell Line
Cricetinae
Fundamental and applied biological sciences. Psychology
Gammaherpesvirus
Genetics
Herpesvirus 8, Human - genetics
HMGB1 Protein - physiology
Humans
Immediate-Early Proteins - physiology
Kaposi's sarcoma-associated herpesvirus
Microbiology
Miscellaneous
Molecular Sequence Data
Murine gammaherpesvirus 68
Response Elements
Rhadinovirus - genetics
Trans-Activators - physiology
Transcriptional Activation
Viral Proteins - physiology
Virology
Virus Replication
Title The DNA Architectural Protein HMGB1 Facilitates RTA-Mediated Viral Gene Expression in Gamma-2 Herpesviruses
URI http://jvi.asm.org/content/78/23/12940.abstract
https://www.ncbi.nlm.nih.gov/pubmed/15542646
https://search.proquest.com/docview/17701002
https://search.proquest.com/docview/67070144
https://pubmed.ncbi.nlm.nih.gov/PMC524970
Volume 78
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