Functional analysis of the orf390 gene of the White Spot Syndrome Virus

orf390 (WSSV449) is a novel apoptosis inhibitor gene in the genome of the White Spot Syndrome Virus (WSSV). In the present study, we focus on the function of orf390 gene. Stable expression of orf390 prevented SF9 insect cells from undergoing actinomycin D-induced apoptosis. ORF390 also rescued the replication of a p35-deficient-mutant (AcMNPVΔp35k/pol+) in SF9 cells. In addition, ORF390 inhibits the activities of caspase-3 and -9 in vivo and in vitro. Here we demonstrate that the anti-apoptotic activity of ORF390 is dependent on two putative caspase-9 cleavage sites (VETD233↓G and LEHD303↓G) and one caspase-3 cleavage site (DEVD272↓G). Our results support the conclusion that these three sites play a key role in the suppression of apoptosis mediated by ORF390. These data further suggest that orf390 encodes a novel anti-apoptotic protein involved in cell survival and apoptosis regulation.