Wu X, Xiao W, Brandsma J L
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
J Virol. 1994 Sep;68(9):6097-102. doi: 10.1128/JVI.68.9.6097-6102.1994.
The present study used the cottontail rabbit papillomavirus DNA-rabbit system to evaluate whether the regulatory genes E1 and E2 and the transforming gene E6 are required for papilloma formation. Frameshift mutations were generated in the individual genes in the context of a full-length cottontail rabbit papillomavirus genome, and the mutant DNAs were intradermally inoculated into domestic rabbits. None of the mutants induced papillomas. Marker rescue experiments confirmed that the defects were due to mutations that we deliberately introduced. Marker rescue also confirmed our previous report that the upstream region of E7 around position 9 was critical for papilloma induction. These results demonstrate that the E1 and E2 regulatory genes as well as the E6 and E7 transforming genes are each required for papilloma formation. Each gene may provide molecular targets for therapeutic intervention.
本研究利用棉尾兔乳头瘤病毒DNA-兔系统来评估乳头瘤形成是否需要调控基因E1和E2以及转化基因E6。在全长棉尾兔乳头瘤病毒基因组背景下,对各个基因产生移码突变,并将突变DNA皮内接种到家兔体内。没有一个突变体诱导出乳头瘤。标记拯救实验证实这些缺陷是由于我们故意引入的突变所致。标记拯救还证实了我们之前的报告,即E7基因9位附近的上游区域对乳头瘤诱导至关重要。这些结果表明,E1和E2调控基因以及E6和E7转化基因对于乳头瘤形成均是必需的。每个基因都可能为治疗干预提供分子靶点。