The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression in gamma-2 herpesviruses

Moon Jung Song, Seungmin Hwang, Wendy Wong, June Round, DeeAnn Martinez-Guzman, Yaron Turpaz, Jie Liang, Ben Wong, Reid C. Johnson, Michael Carey, Ren Sun

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28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12940-12950
Number of pages11
JournalJournal of Virology
Volume78
Issue number23
DOIs
Publication statusPublished - 2004 Dec 1
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Song, M. J., Hwang, S., Wong, W., Round, J., Martinez-Guzman, D., Turpaz, Y., Liang, J., Wong, B., Johnson, R. C., Carey, M., & Sun, R. (2004). The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression in gamma-2 herpesviruses. Journal of Virology, 78(23), 12940-12950. https://doi.org/10.1128/JVI.78.23.12940-12950.2004