Mycophenolic acid inhibits syncytium formation accompanied by reduction of gp120 expression.
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 IC50 values of 0.1 and 0.5 microM, respectively. The reduction of HIV gp120 expression by MPA (1.0 microM) 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.
Ui
Hideaki
H
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Asanuma
Satoshi
S
Chiba
Harumi
H
Takahashi
Atsushi
A
Yamaguchi
Yuichi
Y
Masuma
Rokuro
R
Omura
Satoshi
S
Tanaka
Haruo
H
D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D015726:Giant Cells / Q000187:drug effects* / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009173:Mycophenolic Acid / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120; D009173:Mycophenolic Acid