DNA TOPOMERASE 1 ACTIVITY IN RETROVIRUSES

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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.