Tang Q, Ginsberg H S
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
J Virol. 1994 Apr;68(4):2127-34. doi: 10.1128/JVI.68.4.2127-2134.1994.
Two type 5 adenovirus (Ad5) early region 1a (E1a) mutants, H5in104 and H5dl105, were impaired in viral replication and cell transformation. In addition, these mutants trans dominantly inhibited the frequency with which H5sub309, a phenotypically wild-type mutant, and H5dl520, a high-frequency transformation mutant, transformed CREF cells. Inhibition of transformation varied in proportion to the input ratio of mutant to coinfecting virus. It was found that H5in104, but not H5dl105, could not complement Ad5 E1b mutants that failed to synthesize 19- or 55-kDa E1b product. H5dl105 yielded 10-fold less virus than the wild-type did in 293 cells, which constitutively express E1a and E1b products; similar low yields were also observed with H5in104 and H5dl105 in another E1a- and E1b-expressing transformed cell line, KB16. Marker rescue and DNA sequence analyses, however, indicated that the phenotypes of H5in104 and H5dl105 were the result of their respective E1a mutations. The data presented are the first to demonstrate that mutants of animal viruses can effect dominant interference with the viral function(s) that produce cell transformation.
两种5型腺病毒（Ad5）早期区域1a（E1a）突变体H5in104和H5dl105在病毒复制和细胞转化方面存在缺陷。此外，这些突变体反式显性抑制了表型野生型突变体H5sub309和高频转化突变体H5dl520转化CREF细胞的频率。转化抑制程度与突变体与共感染病毒的输入比例成比例变化。研究发现，H5in104而非H5dl105不能互补无法合成19 kDa或55 kDa E1b产物的Ad5 E1b突变体。在组成性表达E1a和E1b产物的293细胞中，H5dl105产生的病毒比野生型少10倍；在另一种表达E1a和E1b的转化细胞系KB16中，H5in104和H5dl105也观察到类似的低产量。然而，标记拯救和DNA序列分析表明，H5in104和H5dl105的表型是其各自E1a突变的结果。所呈现的数据首次证明动物病毒突变体可对产生细胞转化的病毒功能产生显性干扰。
