Whalen B, Laffin J, Friedrich T D, Lehman J M
Department of Microbiology, Immunology, and Molecular Genetics, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
Exp Cell Res. 1999 Aug 25;251(1):121-7. doi: 10.1006/excr.1999.4572.
The infection of monkey kidney (CV-1) cells with simian virus 40 (SV40) stimulates the cells into successive rounds of DNA synthesis without an intervening mitosis, leading to the acquisition of a >G2 DNA content. To elucidate the role of small t antigen in cell cycle progression and in viral replication during infection, studies were performed using an SV40 mutant (dl888) that lacks the ability to produce small t. Initially dl888-infected cells move through the first S phase at roughly the same rate as wild-type infected cells. Upon reaching G2, however, the dl888-infected cells progressed to >G2 at a reduced rate relative to wild-type. The slower rate of entry into >G2 of dl888-infected cells is associated with a decrease in total pRb and an increase in the ratio of hypophosphorylated to hyperphosphorylated pRb. The expression of cyclin D1 and p27(kip1) were elevated in dl888-infected cells compared to wild-type-infected CV-1 cells. Taken together, these results indicate that small t antigen plays a role in stimulating entry into >G2 in SV40-infected CV-1 cells, possibly by affecting the regulation of key cell cycle proteins.
猴肾（CV - 1）细胞被猿猴病毒40（SV40）感染后，会刺激细胞连续进行多轮DNA合成，而无需中间的有丝分裂，导致细胞获得大于G2期的DNA含量。为了阐明小t抗原在感染过程中细胞周期进程和病毒复制中的作用，研究人员使用了一种缺乏产生小t抗原能力的SV40突变体（dl888）进行研究。最初，被dl888感染的细胞以与野生型感染细胞大致相同的速率经历第一个S期。然而，在进入G2期后，与野生型相比，被dl888感染的细胞进入大于G2期的速率降低。dl888感染细胞进入大于G2期的速率较慢与总pRb的减少以及低磷酸化pRb与高磷酸化pRb的比率增加有关。与野生型感染的CV - 1细胞相比，dl888感染的细胞中细胞周期蛋白D1和p27（kip1）的表达升高。综上所述，这些结果表明小t抗原在刺激SV40感染的CV - 1细胞进入大于G2期方面发挥作用，可能是通过影响关键细胞周期蛋白的调节来实现的。
