DYSREGULATED SURFACE GENE-EXPRESSION FROM DISRUPTED HEPATITIS-B VIRUSGENOMES

During chronic infection by hepatitis B virus, the viral genome freque ntly integrates into the host chromosome, causing gross disruption and rearrangement of the viral DNA. We have obtained data showing that vi ral genomic disruptions which delete the enhancers from the transcribe d region of the viral surface gene can lead to dysregulation of surfac e gene expression at the transcriptional level. Specifically, in cells transfected with such disrupted genomes, there is a decreased amount of transcripts coding for the major form of the surface protein but li ttle change in the amount of transcripts coding for the large surface protein. In these cells, secretion of the surface proteins is blocked in the endoplasmic reticulum-Golgi intermediate compartment, consisten t with previous work from other groups showing that relative overexpre ssion of the large surface protein can block secretion of all forms of the surface protein. Our findings suggest that viral genomic rearrang ements during integration may be a contributing factor in the pathogen esis of ground-glass hepatocytes, which contain large amounts of intra cellular surface proteins as a result of a block in secretion and are frequently seen in the livers of patients with chronic hepatitis B.