Wei Y, Etiemble J, Renard C A, Tiollais P, Buendia M A
Unité de Recombinaison et Expression Génétique, INSERM U163, Institut Pasteur, Paris, France.
J Gen Virol. 1996 Feb;77 ( Pt 2 ):177-82. doi: 10.1099/0022-1317-77-2-177.
We have analysed abnormal virus RNAs produced from integrated woodchuck hepatitis virus (WHV) sequences in two woodchuck liver tumours. Analysis of cDNA clones revealed that these transcripts consisted of rearranged, virus-specific RNAs encoding the WHV surface antigens. In one tumour, transcription was driven by the major preS2/S promoter and terminated at a cryptic poly(A) signal in the 5' end of the P gene, giving rise to a truncated version of the normal viral S message. In contrast, the integrated preS2/S promoter remained silent in the second tumour. The start sites of two abundant WHV transcripts encoding the large and middle surface proteins were localized about 100 bp upstream and 300 bp downstream of the preS1 translation initiation codon, corresponding to minor start sites of the normal surface protein mRNAs in chronically infected liver. Thus, the preS1 promoter, a weak promoter in episomal replicative forms of the virus, was activated in the integrated state in this tumour. Our results indicate that alternative usage of the preS1 or the preS2/S promoter in the integrated state may yield differential production of the three virus surface proteins in woodchuck liver tumours.
我们分析了两只土拨鼠肝肿瘤中由整合的土拨鼠肝炎病毒（WHV）序列产生的异常病毒RNA。对cDNA克隆的分析表明，这些转录本由重排的、编码WHV表面抗原的病毒特异性RNA组成。在一个肿瘤中，转录由主要的前S2/S启动子驱动，并在P基因5'端的一个隐蔽聚腺苷酸化信号处终止，产生了正常病毒S信息的截短版本。相比之下，整合的前S2/S启动子在第二个肿瘤中保持沉默。编码大表面蛋白和中表面蛋白的两种丰富的WHV转录本的起始位点位于前S1翻译起始密码子上游约100 bp和下游约300 bp处，对应于慢性感染肝脏中正常表面蛋白mRNA的次要起始位点。因此，前S1启动子，一种在病毒游离复制形式中较弱的启动子，在该肿瘤的整合状态下被激活。我们的结果表明，整合状态下前S1或前S2/S启动子的交替使用可能导致土拨鼠肝肿瘤中三种病毒表面蛋白的差异产生。
