Furukawa H, Momota K, Agatsuma T, Yamamoto I, Kimura S, Shimada K
Biological Research Laboratories, Sankyo Co. Ltd, Medical Science Institute of University of Tokyo, Japan.
Nucleic Acids Res. 1994 Dec 25;22(25):5621-7. doi: 10.1093/nar/22.25.5621.
Oligodeoxyribonucleotides (ODN) linked at their 5'-end with dimethoxytrityl (DmTr) residue were examined for antiviral activities against human immunodeficiency virus type 1 (HIV-1). We found that guanine-rich oligonucleotides exhibit anti-HIV activity upon 5'-end modification with DmTr. One oligonucleotide, DmTr-TGGGAGGTGGGTCTG (SA-1042), showed potent anti-HIV activity in vitro. A greater than 95% reduction of infectivity was observed if the cells were treated with 10 micrograms/ml of SA-1042 at the time of viral infection, PCR analysis confirmed that there was a significant reduction of provirus in the cells exposed to virus in the presence of SA-1042. By contrast, no inhibition was observed if the cells were treated with the oligomer 1 h after virus adsorption. SA-1042 prevented syncytium formation between chronically infected cells and CD4 positive uninfected cells. Furthermore, the oligomer interfered the interaction of purified gp120 to the CD4 receptor. By contrast, SA-1042 had no inhibitory effect on chronically HIV-infected cells. These results strongly suggest that the DMTr-ODNs with appropriate base sequences antagonize HIV-1 infection during the stage of virus-cell interaction.
对5'-末端连接有二甲氧基三苯甲基（DmTr）残基的寡脱氧核糖核苷酸（ODN）进行了抗1型人类免疫缺陷病毒（HIV-1）活性检测。我们发现富含鸟嘌呤的寡核苷酸在经DmTr进行5'-末端修饰后具有抗HIV活性。一种寡核苷酸，DmTr-TGGGAGGTGGGTCTG（SA-1042），在体外显示出强大的抗HIV活性。如果在病毒感染时用10微克/毫升的SA-1042处理细胞，可观察到感染性降低超过95%，PCR分析证实，在存在SA-1042的情况下，暴露于病毒的细胞中的前病毒显著减少。相比之下，如果在病毒吸附1小时后用该寡聚物处理细胞，则未观察到抑制作用。SA-1042可防止慢性感染细胞与CD4阳性未感染细胞之间形成合胞体。此外，该寡聚物干扰了纯化的gp120与CD4受体的相互作用。相比之下，SA-1042对慢性HIV感染细胞没有抑制作用。这些结果强烈表明，具有适当碱基序列的DMTr-ODN在病毒-细胞相互作用阶段可拮抗HIV-1感染。
