Trans-activation of HLA-DR gene by hepatitis B virus X gene product.

Abstract

(23) and is not expressed on normal human hepatocytes (24). Although aberrant expression of HLA-DR on hepatocytes observed during HBV infection has been suggested to be due to cytokines produced by the adjacent inflammatory cells (24, 25), it is not known whether HBV itself is involved in the induction process. This study demonstrates that transfection of cultured human hepatoma cell lines with genomic HBV sequences can induce HLA-DR expression in vitro in the absence of inflammation. We further show here that the X gene product of HBV alone is capable of inducing transcription of the HLA-DR gene.

Hepatitis B Virus Biology

“…In vitro, X exhibits a plethora of activities. From cell culture studies, it is believed that X can activate the transcription of host genes, including the major histocompatibility complex (94,219,251) and c-myc (4), as well as viral genes (37,192), and one investigator has even reported that X stabilizes viral RNAs (186). Most investigators agree that X is not a DNA binding protein and that it is therefore not a typical transactivator.…”

Hepatitis B Virus X Protein Is a Transcriptional Modulator That Communicates with Transcription Factor IIB and the RNA Polymerase II Subunit 5

“…One of the RNA polymerase III promoters is also transactivated by HBx (12). Several endogenous genes important for cell proliferation and acute inflammatory response, such as c-fos, c-jun, and human interleukin-8, are activated by HBx (3,7,13). This broad gene-regulating function suggests that HBx not only up-regulates the expression of HBV genes by transactivating the HBV enhancer but also modifies the environment by transactivating cellular genes in infected cells to facilitate viral replication.…”

Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX.

“…and cellular (10,23,27,47,56) Phosphorylation and dephosphorylation of c-Fos and c-Jun have been described as posttranslational modifications with a critical role in the regulation of AP1 function. Phosphorylation of the c-Fos C terminus seems to be important for negative autoregulation and for transformation (34,46) but not for transactivation of genes linked to an AP1 site.…”

“…The hepatitis B virus (HBV) X gene encodes a polypeptide of 154 amino acids, with no significant homology with other known proteins, which is capable of transactivating gene expression acting on a wide spectrum of viral (13,28,42,49,55) and cellular (10,23,27,47,56) (8). Moreover, the relative promiscuity of its action suggests that the X protein acts indirectly, modifying the activities of cellular factors that modulate transcription from RNA polymerase II as well as from RNA polymerase III promoters (5,41).…”