The first step in cellular entry of HIV involves binding of the viral envelope glycoprotein complex (gpl20/gp41) to specific receptor molecules on the target cells. The cell-cell fusion (syncytium formation) between env expressing cells and CD4+cells mimics the viral infection of the host cells. To search for anti-HIV substances preventing this process, we constructed the recombinant cell lines, HeLa/CD4/Lac-Z and HeLa/T-env/Tat for T-cell tropic (HIV-1NL4_3) system, and HOS/CD4/CCR5/Lac-Z and HeLa/M-env/Tat for macrophage tropic (HIV-1SF162) system. Wheneach pair of cells were co-incubated for 20 hours, the multinuclear giant cells (syncytia) were formed and /3-galactosidase was expressed. These systems are less
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
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