Inhibition of retrovirus-induced disease in mice by camptothecin.
We have previously shown that noncytotoxic doses of camptothecin (CPT), a topoisomerase I-specific antagonist, inhibit retrovirus replication in acutely and chronically infected cells. To evaluate the efficacy of CPT as an antiretroviral drug in vivo, we injected newborn BALB/c mice with Moloney murine leukemia virus and adult NFS mice with Friend spleen focus-forming virus. The Moloney murine leukemia virus-injected mice developed lymphoma, and the Friend spleen focus-forming virus-injected mice developed erythroleukemia. CPT, administrated together with the virus or 1 or 2 days after virus injection, prevented the onset of the disease in both cases. We showed that repeated CPT treatments increased the effectiveness of the drug when administrated 3 days after virus injection. This ability of CPT to inhibit retrovirus-induced disease in vivo without causing any apparent toxic side effects suggests its application as a legitimate remedy for the treatment of retroviral diseases.
Department of Immunology and Microbiology, Faculty of Health Sciences, Soroka Medical Center, Beer-Sheva, Israel.
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Priel
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Aflalo
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Chechelnitsky
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Benharroch
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Aboud
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Segal
D016475:3T3 Cells; D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002166:Camptothecin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D004915:Leukemia, Erythroblastic, Acute / Q000209:etiology / Q000517:prevention & control; D007942:Leukemia, Experimental / Q000209:etiology / Q000517:prevention & control; D008223:Lymphoma / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000187:drug effects* / Q000254:growth & development; D009374:Neoplasms, Experimental / Q000209:etiology / Q000517:prevention & control*; D012192:Retroviridae Infections / Q000150:complications / Q000188:drug therapy*; D013154:Spleen / Q000473:pathology; D013155:Spleen Focus-Forming Viruses / Q000187:drug effects* / Q000254:growth & development; D014779:Virus Replication
D002166:Camptothecin