The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression 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.
Song
Moon Jung
MJ
Department of Molecular and Medical Pharmacology, Center for Health Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Hwang
Seungmin
S
Wong
Wendy
W
Round
June
J
Martinez-Guzman
Deeann
D
Turpaz
Yaron
Y
Liang
Jie
J
Wong
Ben
B
Johnson
Reid C
RC
Carey
Michael
M
Sun
Ren
R
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D024243:HMGB1 Protein / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D020218:Response Elements; D018144:Rhadinovirus / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication
D024243:HMGB1 Protein; D017874:Immediate-Early Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins