Huleihel M, Marvit J, Aboud M
Int J Cancer. 1983 Jun 15;31(6):737-43. doi: 10.1002/ijc.2910310611.
Mouse interferon (IFN) was found to inhibit murine sarcoma virus (MSV)-induced neoplastic transformation of normal rat kidney (NRK) cells. This effect was observed upon examining the formation of foci of morphologically altered cells and colonies of anchorage-independent cells. IFN had no cytotoxic effect on MSV-transformed NRK cells, nor on their focus or colony-forming ability. It was therefore apparent that its inhibitory effect was directed against the viral role in cell transformation. In attempts to define the mechanism of this effect, we found that IFN delayed the initiation of the cytoplasmic viral DNA synthesis. However, the amount of this DNA eventually formed in IFN-treated cells was the same as in the control cells. Furthermore, the transport of this DNA to the nucleus was slower in IFN-treated cells, although all of it was finally transferred. However, while most of the viral DNA integrated into the genome of the control cells, very little integration occurred in IFN-treated cells. The unintegrated viral DNA of these cells was slowly degraded. Therefore, if the cells recovered from the antiviral effect of IFN when intact viral DNA molecules still existed in their nucleus, they could resume viral DNA integration and cell transformation. IFN was found to block viral DNA supercoiling. Since supercoiled viral DNA is considered to be a precursor to integrated provirus, it seems that the inhibition of both integration and cell transformation is due to this impaired coiling.
已发现小鼠干扰素（IFN）可抑制鼠肉瘤病毒（MSV）诱导的正常大鼠肾（NRK）细胞的肿瘤转化。在检查形态改变的细胞集落和不依赖贴壁细胞的克隆形成时观察到了这种效应。IFN对MSV转化的NRK细胞及其集落形成或克隆形成能力均无细胞毒性作用。因此，很明显其抑制作用是针对病毒在细胞转化中的作用。在试图确定这种效应的机制时，我们发现IFN延迟了细胞质病毒DNA合成的起始。然而，在经IFN处理的细胞中最终形成的这种DNA的量与对照细胞中的相同。此外，在经IFN处理的细胞中，这种DNA向细胞核的转运较慢，尽管最终所有的DNA都被转移了。然而，虽然大多数病毒DNA整合到对照细胞的基因组中，但在经IFN处理的细胞中很少发生整合。这些细胞中未整合的病毒DNA被缓慢降解。因此，如果当完整的病毒DNA分子仍存在于细胞核中时细胞从IFN的抗病毒作用中恢复，它们可能会恢复病毒DNA整合和细胞转化。已发现IFN可阻断病毒DNA超螺旋化。由于超螺旋病毒DNA被认为是整合前病毒的前体，似乎整合和细胞转化的抑制都是由于这种超螺旋受损所致。
