Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours

The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma.     

反式激活HIV-1 LTR的HHV-6基因片段B701的缺失研究

ＨＨＶ－６在体外可以激活ＨＩＶＬＴＲ引导的基因表达［１］，其基因组中一基因片段Ｂ７０１已被证明与这种激活作用有关［２］．Ｂ７０１编码１４３个氨基酸的蛋白质，可与ＨＨＶ－６基因组中其它基因片段协同作用提高对ＨＩＶＬＴＲ的激活效力．对Ｂ７０１进行缺失突变，得到突变体ＲＳＶ－Ｂ７０１－ｄ１（３′端缺失１８１个ｂｐ）、ＲＳＶ－Ｂ７０１－ｄ６（３′端缺失３５３个ｂｐ），将这两个缺失突变体分别与ＨＩＶ－Ｌｕｃ共转染受体细胞，通过ＬＵＣ活性分析发现，缺失突变体ｄ１、ｄ６不但仍具有激活能力，而且ｄ６的激活能力要远远大于ｄ１．二级结构预测初步揭示了Ｂ７０１对ＨＩＶ－ＬＴＲ的反式激活作用机制，为阐明ＨＨＶ－６基因产物与ＡＩＤＳ的病理关系提供了依据．