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Journal of Virology, December 2004, p. 12940-12950, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.12940-12950.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Moon Jung Song,1 Seungmin Hwang,1 Wendy Wong,1 June Round,1 DeeAnn Martinez-Guzman,1 Yaron Turpaz,2 Jie Liang,2 Ben Wong,3 Reid C. Johnson,3 Michael Carey,3 and Ren Sun1*

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, Illinois2

Received 28 February 2004/ Accepted 26 July 2004

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.

* 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{at}mednet.ucla.edu.

Journal of Virology, December 2004, p. 12940-12950, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.12940-12950.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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