Document 3322 DOCN M94A3322 TI Inhibitory mechanism of camptothecin on HIV-1 replication. DT 9412 AU Takahashi H; Kojima A; Kurata T; Dep. of Pathology, National Institute of Health, Tokyo, Japan. SO Int Conf AIDS. 1994 Aug 7-12;10(1):102 (abstract no. PA0028). Unique Identifier : AIDSLINE ICA10/94369253 AB OBJECTIVES--Camptothecin (CPT), a topoisomerase I inhibitor was reported to block retroviral infection in vitro and in vivo. CPT is also known as an antitumor drug and is toxic to eukaryotic cells. As HIV-1 replicates very poorly in non-dividing cells, CPT inhibits HIV possibly by suppressing cell growth, otherwise it may attack virion directly. Our object is to know inhibitory effects of CPT on HIV and to understand a role of topoisomerase I on HIV-1 replication. METHODS--HIV-1 viruses were treated with CPT for 1-2 hours. The pretreated viruses were infected to MT4 cells in the presence or absence of CPT. HIV-1 replication was measured by p24 ELISA and RT assays. RESULTS AND DISCUSSION--Pretreatment of HIV-1 with CPT inhibited viral replication in a dose-dependent fashion. Presence of CPT during infection showed higher blocking of HIV-1 replication. Reduction of topoisomerase I activity in infected MT-4 cells by CPT was associated with decrease of HIV-1 infectivity. These results suggested that both virion-associated and cellular topoisomerase I play a regulatory role of HIV-1 replication. DE Camptothecin/*PHARMACOLOGY Cell Division/DRUG EFFECTS Cell Line DNA Topoisomerase/ANTAGONISTS & INHIB/PHYSIOLOGY Human HIV Core Protein p24/BIOSYNTHESIS HIV-1/*DRUG EFFECTS/ENZYMOLOGY/PHYSIOLOGY In Vitro Reverse Transcriptase/BIOSYNTHESIS Virus Replication/*DRUG EFFECTS/PHYSIOLOGY MEETING ABSTRACT SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).