An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs

Two different baculovirus genes are known to be able to block apoptosis triggered upon infection of Spodoptera-frugiperda cells with p35 mutants of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV): p35 (P35-encoding gene) of AcMNPV (R.J. Clem, M. Fechheimer, and L.K. Miller, Science 254:1388-1390,1991) and iap (inhibitor of apoptosis gene) of Cydia pomonella granulosis virus (CPGV) (N.E. Crook. R.J. Clem, and L.K. Miller, J. Virol. 67:2168-2174, 1993). Using a genetic complementation assay to identify additional genes which inhibit apoptosis during infection with ap35 mutant, we have isolated a gene from Orgyia pseudotsugata NPV (Op-iap) that was able to functionally substitute for AcMNPV p35. The nucleotide sequence of this gene, Op-iap, predicted a 30-kDa polypeptide product with approximately 58% amino acid sequence identity to the product of CpGV iap, Cp-IAP. Like Cp-IAP, the predicted product of Op-iap has a carboxy-terminal C3HC4 zinc finger-like motif In addition, a pair of additional cysteine/histidine motifs were found in the N-terminal regions of both polypeptide sequences. Recombinant p35 mutant viruses carrying either Op-iap or Cp-iap appeared to have a normal phenotype in S. frugiperda cells. Thus, Cp-IAP and Op-IAP appear to be functionally analogous to P35 but are likely to block apoptosis by a different mechanism which may involve direct interaction with DNA