학술논문

Regulation of Hepatitis B Virus Replication by the Ras-Mitogen-Activated Protein Kinase Signaling Pathway.
Document Type
Article
Source
Journal of Virology. Jul2003, Vol. 77 Issue 14, p7707. 6p. 7 Graphs.
Subject
*RAS oncogenes
*HEPATITIS B virus
*GUANOSINE triphosphatase
*VIRAL replication
*TRANSCRIPTION factors
Language
ISSN
0022-538X
Abstract
The replication of hepatitis B virus (HBV) can be regulated by a variety of factors, including hormones, growth factors, and cytokines. However, the molecular mechanisms of these regulations are largely unknown. Ras is a small GTPase that responds to many of these external stimuli. In this study, we investigated the possible effect of Ras on the replication of HBV. Our results indicated that activated Ras could suppress the replication of HBV in both Huh7 and HepG2 cells. This suppression was independent of the X protein and most likely occurred at the transcriptional level. Deletion-mapping analysis of the HBV core promoter and its upstream ENI and ENII enhancers revealed multiple elements responsive to activated Ras. This suppression of HBV replication by activated Ras was apparently mediated by the mitogen-activated protein (MAP) kinase pathway, as it was accompanied by activation of ERK½ and abolished by the MEK½ inhibitor U0126. Our results thus indicate that external stimuli may suppress HBV replication through the Ras-MAP kinase pathway. [ABSTRACT FROM AUTHOR]