TY - JOUR
T1 - The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression in gamma-2 herpesviruses
AU - Moon, Jung Song
AU - Hwang, Seungmin
AU - Wong, Wendy
AU - Round, June
AU - Martinez-Guzman, Dee Ann
AU - Turpaz, Yaron
AU - Liang, Jie
AU - Wong, Ben
AU - Johnson, Reid C.
AU - Carey, Michael
AU - Sun, Ren
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=8644232572&partnerID=8YFLogxK
U2 - 10.1128/JVI.78.23.12940-12950.2004
DO - 10.1128/JVI.78.23.12940-12950.2004
M3 - Article
C2 - 15542646
AN - SCOPUS:8644232572
SN - 0022-538X
VL - 78
SP - 12940
EP - 12950
JO - Journal of virology
JF - Journal of virology
IS - 23
ER -