Van Hille B, Duponchel N, Salomé N, Spruyt N, Cotmore S F, Tattersall P, Cornelis J J, Rommelaere J
Laboratory of Molecular Oncology, INSERM U186, Lille, France.
Virology. 1989 Jul;171(1):89-97. doi: 10.1016/0042-6822(89)90514-x.
The FR3T3 and NRK rat cell lines and their human EJ Ha-ras-1 oncogene-transformed derivatives, termed FREJ and NREJ, were compared for their susceptibility to the parvovirus MVMp. For a similar production of p21ras protein, FREJ clones are markedly sensitized to killing by MVMp, whereas the NREJ cells are not. Such a contrasting effect of ras transformation on the sensitivity of cells of different origins to MVMp can be traced back to their respective abilities to support the parvoviral life cycle. The FR3T3 line produces a substantial amount of viral DNA whose expression in the form of the nonstructural protein NS-1 is stimulated in its transformed derivatives. Conversely, NRK cells offer an early block to parvoviral DNA replication and expression that appears to persist in the ras-transformed clones. Thus, at least two intracellular restrictions can protect normal rat cells against MVMp infection, and transformation by ras relieves one of them at the level of parvoviral gene expression. A fair correlation was also found between the degree of sensitivity of the various lines to MVMp-induced killing and their capacity to synthesize the nonstructural viral proteins, suggesting a possible role of parvoviral nonstructural proteins in cytotoxicity.
对FR3T3和NRK大鼠细胞系及其经人EJ Ha-ras-1癌基因转化的衍生物（分别称为FREJ和NREJ）对细小病毒MVMp的敏感性进行了比较。对于相似的p21ras蛋白产量，FREJ克隆对MVMp杀伤明显敏感，而NREJ细胞则不然。ras转化对不同来源细胞对MVMp敏感性的这种对比效应可追溯到它们各自支持细小病毒生命周期的能力。FR3T3细胞系产生大量病毒DNA，其以非结构蛋白NS-1形式的表达在其转化衍生物中受到刺激。相反，NRK细胞对细小病毒DNA复制和表达提供早期阻滞，这一阻滞在ras转化的克隆中似乎持续存在。因此，至少有两种细胞内限制可保护正常大鼠细胞免受MVMp感染，而ras转化在细小病毒基因表达水平上解除了其中一种限制。还发现各细胞系对MVMp诱导杀伤的敏感程度与其合成病毒非结构蛋白的能力之间存在合理的相关性，这表明细小病毒非结构蛋白在细胞毒性中可能起作用。
