Suruga Y, Makino M, Okada Y, Tanaka H, De Clercq E, Baba M
Center for Chronic Viral Diseases, First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 1;18(4):316-22. doi: 10.1097/00042560-199808010-00002.
LP-BM5 murine leukemia virus (MuLV) infection causes severe immunodeficiency termed murine AIDS (MAIDS). The acyclic nucleoside phosphonates, (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were examined, in comparison with zidovudine (AZT), for their inhibitory effect on the development of MAIDS. Although no significant difference in inhibition of LP-BM5 MuLV replication was identified between PMPA and PMEA in cell cultures, PMPA was obviously less cytotoxic to the host lymphocytes. None of the mice treated in vivo with 5 or 25 mg/kg of PMPA or 25 mg/kg of PMEA developed MAIDS at 5 weeks after viral infection. However at 9 weeks, none of the 25 mg/kg PMPA-treated mice progressed to MAIDS, except for one that developed mild MAIDS, whereas PMEA, even at 100 mg/kg, could not prevent disease progression. MAIDS-associated activation of lymphocytes and viral replication were drastically inhibited by PMPA treatment. These results indicate that PMPA is a highly effective antiretroviral agent in vivo.
