INHIBITION OF SMALL RUMINANT LENTIVIRUS BY ANTIVIRAL DRUGS

ABSTRACT Inhibitors of the reverse transcriptase and protease enzymes were evaluated for their inhibitory effect on the replication of caprine arthritis encephalitis virus (CAEV) strain CAEV Cork and of the Maedi-Visna virus (MVV) strain K1514 cultured in fibroblastic cells. The drugs lamivudine, didanosine, stavudine, zidovudine, efavirenz, atazanavir and lopinavir/ritonavir were used. The highest concentration used for lamivudine, stavudine, zidovudine and efavirenz was 500 ?M, for atazanavir it was 50 ?M and 5.0 ?M for lopinavir/r and didanosine. The in vitro antiviral activity was investigated by evaluating the cell viability by the MTT method and testing for inhibition of cytopathic effects (CPE) of the virus. The replication of the virus was not completely inhibited by the protease inhibitors atazanavir and lopinavir/r in the test for CPE, while the others drugs showed significant antiviral efficacy in different concentrations. The protease inhibitors together with the efavirenz did not show antiviral activity when they were assessed by the reduced MTT technique. These data showed that the reverse transcriptase inhibitor drugs lamivudine, didanosine, stavudine and zidovudine were effective in the in vitro inhibition of small ruminant lentivirus.

摘要
本研究评估了逆转录酶（reverse transcriptase）与蛋白酶（protease）抑制剂对成纤维细胞（fibroblastic cells）中培养的山羊关节炎脑炎病毒（caprine arthritis encephalitis virus, CAEV）毒株CAEV Cork及梅迪-维斯纳病毒（Maedi-Visna virus, MVV）毒株K1514复制过程的抑制效果。本次实验选用的受试药物包括拉米夫定（lamivudine）、去羟肌苷（didanosine）、司他夫定（stavudine）、齐多夫定（zidovudine）、依非韦伦（efavirenz）、阿扎那韦（atazanavir）以及洛匹那韦/利托那韦（lopinavir/ritonavir）。其中，拉米夫定、司他夫定、齐多夫定及依非韦伦的最高实验浓度为500 μM，阿扎那韦为50 μM，洛匹那韦/利托那韦与去羟肌苷的最高实验浓度则为5.0 μM。本研究通过MTT法检测细胞存活率，并评估病毒诱导的细胞病变效应（cytopathic effects, CPE）抑制情况，以探究受试药物的体外抗病毒活性。在CPE检测中，蛋白酶抑制剂阿扎那韦与洛匹那韦/利托那韦无法完全抑制病毒复制，其余药物在不同浓度下均表现出显著的抗病毒活性。当采用MTT还原法进行评估时，蛋白酶抑制剂与依非韦伦联用未表现出抗病毒活性。上述实验数据表明，逆转录酶抑制剂类药物拉米夫定、去羟肌苷、司他夫定及齐多夫定可在体外有效抑制小反刍动物慢病毒的复制。