The baculovirus antiapoptotic p35 gene also functions via an oxidant-dependent pathway

Cellular imbalance in the levels of antioxidants and reactive oxygen specie s resulting in apoptosis is directly associated with a number of parasitic infections, aging, and several genetic and multifactorial diseases. The bac ulovirus AcNPV-encoded antiapoptotic p35 gene prevents apoptosis induced by a variety of apoptotic agents in different systems. We demonstrate the abi lity of the p35 gene to inhibit oxidative stress-induced apoptosis. In vitr o cultured Spodoptera frugiperda (Sf9) insect cells infected with wild-type AcNPV carrying the antiapoptotic p35 gene did not undergo apoptosis when s ubjected to oxidative stress generated by the exogenous application of oxid ants or in vivo generation of reactive oxygen species or on direct exposure of cells to UV radiations, An AcNPV mutant carrying a deletion of the p35 gene failed to arrest cell death, Transfection of cells with a recombinant plasmid containing the p35 gene under the transcriptional control of a stre ss promoter (Drosophila hsp70) was also able to rescue cells from oxidative stress-induced cell death, demonstrating the direct involvement of P35. ES R spin-trapping studies conducted in vitro and in vivo demonstrated that P3 5 functions directly as an antioxidant by mopping out free radicals and con sequently prevents cell death by acting at an upstream step in the reactive oxygen species-mediated cell death pathway.