X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis

Hepatitis B virus produces chronic infections or the liver leading to cirrhosis and hepatocellular carcinoma. The X protein of hepatitis B virus (HBx) is a multifunctional protein that can interact with p53 but can also influence a variety of signal transduction pathways within the cell. in most instances this small viral protein favors cell survival and probably initiates hepatocarcinogenesis. HBx upregulates the activity of a number of transcription factors including NF-kappaB. AP-1. CREB. and TBP. However. the majority of HBx is localized to the cytoplasm where it interacts with and stimulates protein kinases such as protein kinase C. Janus kinase/STAT. 1KK. PI-3-K. stress-activated protein kinase/Jun N-terminal kinase, and protein kinase B/Akt. This small viral protein can localize to the mitochondrion. HBx may act as an adaptor or kinase activator to influence signal transduction pathways. This review will, attempt to analyze the involvement of HBx in signal transduction pathways during hepatitis B viral infections and hepatocellular carinoma development. (C) 2001 Elsevier Science Ltd. All rights reserved.