
<ArticleTitle>Subcellular localisation of the <prot>X protein</prot> in HBV infected hepatocytes.</ArticleTitle>
<AbstractText>Hepatitis B virus <prot>X protein</prot> (<prot>HBx</prot>) is a multifunctional protein that exerts its effects primarily by acting as a transcriptional transactivator of viral and multiple host cell genes. <prot>HBx</prot> is thought to be essential for maintaining viral replication and has been implicated in the development of hepatocellular carcinoma in patients chronically infected with hepatitis B virus. Very little is known about its functional mechanisms and although interactions with several nuclear and cytoplasmic proteins have been demonstrated in vitro, there is no clear consensus as to where <prot>HBx</prot> localises in infected hepatocytes. In this study, the expression and intracellular distribution of <prot>HBx</prot> were examined in human liver biopsies using an anti-<prot>HBx</prot> rabbit polyclonal antiserum. <prot>HBx</prot> was detected in a high proportion (69%) of samples from patients with chronic HBV infection. Detection of <prot>HBx</prot> correlated with the absence of cirrhosis and the presence of serum e-antigen. <prot>HBx</prot> was detected predominantly in the cytoplasm; however, it was also found in the nuclei of up to 20% of positively stained hepatocytes, either exclusively nuclear or localised both in the nucleus and cytoplasm within the same cell. Furthermore, the intracellular distribution of <prot>HBx</prot> was analysed in transfected Huh-7 cells by confocal microscopy, using the monoclonal antibody 16F1. In these experiments, a substantial nuclear detection was confirmed in a significant proportion of <prot>HBx</prot> expressing cells. The data indicate a high functional significance of nuclear <prot>HBx</prot>, consistent with the concept that transactivation may involve interactions with nuclear proteins.</AbstractText>
