Egberink H, Borst M, Niphuis H, Balzarini J, Neu H, Schellekens H, De Clercq E, Horzinek M, Koolen M
Department of Infectious Diseases and Immunology, School of Veterinary Medicine, State University of Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 1990 Apr;87(8):3087-91. doi: 10.1073/pnas.87.8.3087.
The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice. In the latter system PMEA has stronger antiretroviral potency and selectivity than 3'-azido-3'-thymidine (AZT). We have now investigated the effect of the drug in cats infected with the feline immunodeficiency virus (FIV). In vitro, PMEA was found to efficiently block FIV replication in feline thymocytes (50% effective dose, 0.6 microM). When administered to cats at doses of 20, 5, or 2 mg/kg per day, PMEA caused a dose-dependent suppression of FIV replication and virus-specific antibody production. Seropositive field cats with signs of opportunistic infection (gingivitis, stomatitis, and diarrhea) showed clinical improvement during PMEA therapy (5 mg/kg per day) and recurrence of the disease after treatment was discontinued. Thus, FIV infection in cats is an excellent model to test the efficacy of selective anti-human immunodeficiency virus agents in vivo.
无环嘌呤核苷类似物9-(2-膦酰甲氧基乙基)腺嘌呤[PMEA；以前称为9-(2-膦酰基甲氧基乙基)腺嘌呤]是一种在体外对人类免疫缺陷病毒复制以及对小鼠莫洛尼氏鼠肉瘤病毒诱导的肿瘤形成具有强效和选择性抑制作用的药物。在后者的系统中，PMEA比3'-叠氮-3'-胸苷(AZT)具有更强的抗逆转录病毒效力和选择性。我们现在研究了该药物对感染猫免疫缺陷病毒(FIV)的猫的作用。在体外，发现PMEA能有效阻断猫胸腺细胞中的FIV复制(50%有效剂量，0.6微摩尔)。当以每天20、5或2毫克/千克的剂量给猫给药时，PMEA引起FIV复制和病毒特异性抗体产生的剂量依赖性抑制。有机会性感染迹象(牙龈炎、口腔炎和腹泻)的血清阳性野外猫在PMEA治疗期间(每天5毫克/千克)显示出临床改善，停药后疾病复发。因此，猫的FIV感染是在体内测试选择性抗人类免疫缺陷病毒药物疗效的一个极佳模型。
