DNA TOPOMERASE 1 ACTIVITY IN RETROVIRUSES

以前，拓扑异构酶I活性的存在，在艾滋病毒和其他 慢病毒颗粒被报道，并显示与 病毒核衣壳（NC）蛋白。 目前已获得数据， 表明纯化的HIV NC（p7）可以结合并松弛超螺旋， 质粒DNA。 此外，当p7与单链 质粒DNA，病毒p7和DNA磷酸基团之间的共价键， 被发现。 弛豫和共价键的形成都已被证明 是拓扑异构酶作用机制的一部分。 已经表明拓扑异构酶I抑制剂喜树碱可以 阻断HIV感染人类T细胞的效率高达90%。 一 已经产生了CEM细胞的CPT抗性系，其表达一种 耐药拓扑异构酶I活性。 CPT抑制HIV感染 在这些细胞中（CEM-R）比在亲本细胞上更有效。 艾滋病毒 在CEM-R细胞上生长的细胞似乎也发生了改变， 相对于其感染其它CEM-R细胞能力， 野生型CEM或HeLa T4+细胞。

Previously, the presence of topoisomerase I activity in HIV and other lentivirus particles was reported and shown to be associated with the viral nucleocapsid (NC) protein. Data has now been obtained which indicates that purified HIV NC (p7) can bind to and relax supercoiled plasmid DNA. Furthermore, when p7 is incubated with single-stranded plasmid DNA, a covalent bond between viral p7 and DNA phosphate groups can be detected. Both relaxation and covalent bond formation have been shown to be part of the mechanism of topoisomerase action. It has been shown that the topoisomerase I inhibitor, camptothecin, can block HIV infection of human T-cells with efficiencies as high as 90%. A CPT-resistant line of CEM cells has been generated, which expresses a drug-resistant topoisomerase I activity. CPT inhibition of HIV infection in these cells (CEM-R) is more efficient than on parental cells. HIV grown on CEM-R cells also appears to be altered in that its ability to infect other CEM-R cells is reduced, relative to its ability to infect wild-type CEM's or HeLa T4+ cells.