BACULOVIRUS P35 PREVENTS DEVELOPMENTALLY PROGRAMMED CELL-DEATH AND RESCUES A CED-9 MUTANT IN THE NEMATODE CAENORHABDITIS-ELEGANS

Programmed cell death, or apoptosis, occurs throughout the course of n ormal development in most animals and can also be elicited by a number of stimuli such as growth factor deprivation and viral infection. Cer tain morphological and biochemical characteristics of programmed cell death are similar among different tissues and species. During developm ent of the nematode Caenorhabditis elegans, a single genetic pathway p romotes the death of selected cells in a lineally fixed pattern. This pathway appears to be conserved among animal species. The baculovirus p35-encoding gene (p35) is an inhibitor of virus-induced apoptosis in insect cells. Here we demonstrate that expression of p35 in C. elegans prevents death of cells normally programmed to die. This suppression of developmentally programmed cell death results in appearance of extr a surviving cells. Expression of p35 can rescue the embryonic lethalit y of a mutation in ced-9, an endogenous gene homologous to the mammali an apoptotic suppressor bcl-2, whose absence leads to ectopic cell dea ths. These results support the hypothesis that viral infection can act ivate the same cell death pathway as is used during normal development and suggest that baculovirus p35 may act downstream or independently of ced-9 in this pathway.