Baculovirus-based genetic screen for antiapoptotic genes identifies a novel IAP

The prototype baculovirus, Autographa californica multiple nuclear polyhedr osis virus (AcMNPV) expresses p35, a potent anti cell-death gene that promo tes the propagation of the virus by blocking host cell. apoptosis. Infectio n of insect Sf-21 cells with AcMNPV lacking p35 induces apoptosis. We have used this pro-apoptotic property of the p35 null virus to screen for genes encoding inhibitors of apoptosis that rescue cells infected with the p35 de fective virus. We report here the identification of Tn-IAP1, a novel member of the IAP family of cell. death inhibitors. Tn-IAP1 blocks cell death ind uced by p35 null AcMNPV, actinomycin D, and Drosophila cell-death inducers KID and GRIM. Given the conserved nature of the cell death pathway, this ge netic screen can be used for rapid identification of novel inhibitors of ap optosis from diverse sources.