Huang Z M, Yen T S
Department of Pathology 113B, Veterans Affairs Medical Center, San Francisco, California.
J Virol. 1993 Dec;67(12):7032-40. doi: 10.1128/JVI.67.12.7032-7040.1993.
During chronic infection by hepatitis B virus, the viral genome frequently integrates into the host chromosome, causing gross disruption and rearrangement of the viral DNA. We have obtained data showing that viral genomic disruptions which delete the enhancers from the transcribed region of the viral surface gene can lead to dysregulation of surface 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 little 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, consistent with previous work from other groups showing that relative overexpression of the large surface protein can block secretion of all forms of the surface protein. Our findings suggest that viral genomic rearrangements during integration may be a contributing factor in the pathogenesis of ground-glass hepatocytes, which contain large amounts of intracellular surface proteins as a result of a block in secretion and are frequently seen in the livers of patients with chronic hepatitis B.
在乙型肝炎病毒慢性感染期间，病毒基因组经常整合到宿主染色体中，导致病毒DNA的严重破坏和重排。我们已获得的数据表明，从病毒表面基因转录区域删除增强子的病毒基因组破坏可导致转录水平上表面基因表达的失调。具体而言，在用此类破坏的基因组转染的细胞中，编码主要表面蛋白形式的转录本数量减少，但编码大表面蛋白的转录本数量变化不大。在这些细胞中，表面蛋白的分泌在内质网-高尔基体中间区室被阻断，这与其他研究小组之前的工作一致，即大表面蛋白的相对过表达可阻断所有形式表面蛋白的分泌。我们的研究结果表明，整合过程中的病毒基因组重排可能是毛玻璃样肝细胞发病机制中的一个促成因素，毛玻璃样肝细胞由于分泌受阻而含有大量细胞内表面蛋白，并且在慢性乙型肝炎患者的肝脏中经常可见。
