Mycophenolic Acid Inhibits Syncytium Formation Accompanied by Reduction of gp120 Expression

Abstract

Mycophenolic acid (MPA) was identified as an inhibitor of syncytium formation during the screening of human immunodeficiency virus (HIV) entry inhibitors. MPA is a well-known inhibitor of inosine monophosphate dehydrogenase and anti-HIV activity has been reported in vitro and in vivo. MPA inhibited syncytium formation in T cell-tropic and macrophage-tropic systems with IC 50 values of 0.1 and 0.5 m M, respectively. The reduction of HIV gp120 expression by MPA (1.0 mM) was observed by use of Western blot analysis. Furthermore, the addition of guanosine restored both syncytium formation and gp120 expression in the presence of MPA. These results suggest that MPA inhibits not only reverse transcription by depletion of a substrate, GTP, as has been reported, but also syncytium formation through a predominant reduction in the amount of gp120 that is vigorously expressed in the above transformed cells and may be in HIV-infected cells.Keywords AIDS, HIV, fusion, gp120, mycophenolic acid, syncytium formation IntroductionDuring the course of screening for new inhibitors against HIV entry to cells using a syncytium formation assay with HIV env-expressing cells and HIV receptor-expressing cells

Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity

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Penicacids H–J, three new mycophenolic acid derivatives from the marine-derived fungus Rhizopus oryzae

“…13 Since its rst report, MPA and its derivatives have been hot research topics due to their vast array of bioactivities ranging from antibacterial, antifungal, antiviral, antitumor to immunosuppressive aspects. [14][15][16][17] Mycophenolate mofetil (MMF), a 2-morpholinoethyl ester prodrug of MPA, is a potent inhibitor of inosine-5 0 -monophosphate dehydrogenase (IMPDH) that is a crucial rate-limiting enzyme in the purine metabolic pathway. IMPDH inuences numerous cellular processes such as replication, transcription and signaling.…”