The effect of human bcl-2 and bcl-X genes on dengue virus-induced apoptosis in cultured cells

Infection of dengue viruses (DENs) can cause human dengue fever, hemorrhagi c fever, or shock syndrome. Although DEN-induced apoptosis has been implica ted in pathogenesis of the DEN-related diseases, the underlying mechanism r emains largely unexplored. In this study, we investigated the effect of ect opic expression of human bcl-2 and bcl-X genes on DEN-induced apoptosis in cultured cells. We employed a human isolate of DEN serotype 2 (DEN-2), PL04 6, which not only caused cell-cycle arrest in the G1 phase but also induced apoptosis in infected baby hamster kidney (BHK-21) cells, murine neuroblas toma N18 cells, and human neuronal NT-2 cells. Our results reveal that over expression of bcl-2 in fibroblast-like BHK-21 cells, although not inhibitin g virus yields, delayed the process of DEN-induced apoptosis, thereby permi tting surviving cells to become persistently infected. In contrast, stable bcl-2 expression in neuronal N18 cells failed to block DEN-induced apoptosi s. On the other hand, Bcl-X-L, expressed predominantly in the nervous syste m, appeared to delay DEN's killing effect in neuronal N18 cells but not in fibroblast-like BHK-21 cells. In addition, inducible expression bcl-X,, des pite its proapoptotic property in other reported system, was found to merel y accelerate cell death in DEN-infected N18 but not in infected BHK-21 cell s. Thus, through studying the effect of human bcl-2-related genes, our resu lts suggest that DEN infection may trigger target cells to undergo morpholo gically similar but biochemically distinct apoptotic pathways in a cell-spe cific manner. (C) 2001 Academic Press.