Wei Y, Ponzetto A, Tiollais P, Buendia M A
Unité de Recombinaison et Expression génétique, INSERM-U.163, Institut Pasteur, Paris.
Res Virol. 1992 Mar-Apr;143(2):89-96. doi: 10.1016/s0923-2516(06)80086-5.
Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.
土拨鼠肝炎病毒（WHV）是一种小型的、部分双链DNA病毒。与相关的人类乙型肝炎病毒（HBV）一样，WHV在其自然宿主中可诱发急性和慢性肝炎以及肝细胞癌（HCC）。此前在土拨鼠肝癌中已报道过WHV DNA整合到c-myc和N-myc中，导致这些基因的表达失调。我们分析了一个土拨鼠肝肿瘤，其中WHV DNA整合到了c-myc基因中。病毒插入导致一个c-myc等位基因发生多处改变，可能涉及继发性缺失和突变。整合的病毒DNA，包括启动子和增强子序列，起到了插入诱变剂的作用，导致大小从7.2至14 kb不等的异源c-myc转录本表达增强，明显长于正常的2.3 kb c-myc RNA。这些结果提供了另一个例子，即WHV插入的顺式作用效应导致myc基因的致癌激活可能在病毒诱导的土拨鼠肝癌中起关键作用。
