Ueda K, Wei Y, Ganem D
Howard Hughes Medical Institute, University of California Medical Center, San Francisco 94143, USA.
Virology. 1996 Mar 1;217(1):413-7. doi: 10.1006/viro.1996.0133.
Woodchuck hepatitis virus (WHV) is strongly oncogenic in its native host, producing hepatocellular carcinomas in the majority of chronically infected animals. An important step in this oncogenic process is the activation of N-myc transcription in the liver as a result of integration of viral sequences in cis to the N-myc2 locus. We have examined the viral sequences involved in the up-regulation of N-myc2 using transient transfection assays of permissive HepG2 cells in culture. WHV sequences corresponding to enhancer I of human hepatitis B virus are nearly inactive in N-myc2 activation when tested alone and are not significantly activated by WHV X gene coexpression. By contrast, sequences corresponding to enhancer II strongly activate expression in a position and orientation-independent manner and are only modestly further up-regulated by WHx expression. Qualitatively similar results were observed with sequences of the ground squirrel hepatitis virus (GSHV), which produces hepatomas in woodchucks without insertional activation of N-myc2, but the GSHV EnII element is fourfold less active in N-myc2 up-regulation than its WHV counterpart.
土拨鼠肝炎病毒（WHV）在其天然宿主中具有很强的致癌性，在大多数慢性感染的动物中会引发肝细胞癌。这一致癌过程中的一个重要步骤是，由于病毒序列顺式整合到N-myc2基因座，导致肝脏中N-myc转录激活。我们利用培养的允许性HepG2细胞进行瞬时转染试验，研究了参与N-myc2上调的病毒序列。单独测试时，与人类乙型肝炎病毒增强子I相对应的WHV序列在激活N-myc2方面几乎没有活性，并且不会因WHV X基因共表达而被显著激活。相比之下，与增强子II相对应的序列以位置和方向独立的方式强烈激活表达，并且仅被WHx表达适度进一步上调。用松鼠肝炎病毒（GSHV）的序列观察到了定性相似的结果，该病毒在土拨鼠中产生肝癌，但不会对N-myc2进行插入激活，不过GSHV EnII元件在上调N-myc2方面的活性比其对应的WHV元件低四倍。
