CELL TYPE-DEPENDENT EFFECT OF SODIUM VALPROATE ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN-VITRO

Sodium valproate (VPA), a simple branched-chain fatty acid that has an ticonvulsant activity and is used in the treatment of many forms of ep ilepsy, has been reported to stimulate human immunodeficiency virus (H IV) type 1 replication in acutely infected CEM and chronically infecte d U1 cells (Chemico-Biological Interactions 1994;91:111-121). When att empting to reproduce and extend these findings, we confirmed that VPA is able to stimulate HIV-1(IIIB) replication in acutely infected CEM a nd C8166 T lymphocytic cell lines and chronically infected ACH-2 and U 937/IIIB/LAI cells in a concentration-dependent manner. The stimulator y effect of VPA on HIV replication in CEM cells was not increased by p retreatment of the cells with VPA for 24 hr before infection, However, we could not detect any stimulatory effect of VPA on HIV-1(IIIB) repl ication in acutely infected peripheral blood mononuclear cells (PBMCs) , MT-4, MT-2, HUT-78, and MOLT-4 (clone 8) cells and in chronically in fected HUT-78/IIIB/LAI cells, The stimulatory effect by WA under certa in conditions (see above) may be ascribed to an enhanced EW transcript ion, as WA was found to enhance the HIV long terminal repeat (LTR)-dir ected expression of beta-galactosidase in transiently transfected HLta t, P4, and COS7 cells. VPA did not enhance beta-galactoside expression mediated by the cytomegalovirus (CMV) promoter, WA did not affect HIV -induced syncytium formation, Nor had VPA any direct inactivating effe ct on HIV.