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

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

Research output: Contribution to journalArticlepeer-review

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
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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