title: Host insect inhibitor-of-apoptosis SfIAP functionally replaces baculovirus IAP but is differentially regulated by Its N-terminal leader.
abstract: The inhibitor-of-apoptosis (IAP) proteins encoded by baculoviruses bear a striking resemblance to the cellular IAP homologs of their invertebrate hosts. By virtue of the acquired selective advantage of blocking virus-induced apoptosis, baculoviruses may have captured cellular IAP genes that subsequently evolved for virus-specific objectives. To compare viral and host IAPs, we defined antiapoptotic properties of SfIAP, the principal cellular IAP of the lepidopteran host Spodoptera frugiperda. We report here that SfIAP prevented virus-induced apoptosis as well as viral Op-IAP3 (which is encoded by the Orgyia pseudotsugata nucleopolyhedrovirus) when overexpressed from the baculovirus genome. Like Op-IAP3, SfIAP blocked apoptosis at a step prior to caspase activation. Both of the baculovirus IAP repeats (BIRs) were required for SfIAP function. Moreover, deletion of the C-terminal RING motif generated a loss-of-function SfIAP that interacted and dominantly interfered with wild-type SfIAP. Like Op-IAP3, wild-type SfIAP formed intracellular homodimers, suggesting that oligomerization is a functional requirement for both cellular and viral IAPs. SfIAP possesses a ∼100-residue N-terminal leader domain, which is absent among all viral IAPs. Remarkably, deletion of the leader yielded a fully functional SfIAP with dramatically increased protein stability. Thus, the SfIAP leader contains an instability motif that may confer regulatory options for cellular IAPs that baculovirus IAPs have evolved to bypass for maximal stability and antiapoptotic potency. Our findings that SfIAP and viral IAPs have common motifs, share multiple biochemical properties including oligomerization, and act at the same step to block apoptosis support the hypothesis that baculoviral IAPs were derived by acquisition of host insect IAPs.
authors.affiliation: Institute for Molecular Virology, Department of Biochemistry, Graduate School and College of Agricultural and Life Sciences, University of Wisconsin-Madison, 1525 Linden Dr., Madison, WI 53706-1596, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cerio
authors.forename: Rianna
authors.initials: R
authors.lastname: Vandergaast
authors.forename: Paul D
authors.initials: PD
authors.lastname: Friesen
mesh_terms: D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae / Q000235:genetics*; D016679:Genome, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D055550:Protein Stability; D018411:Spodoptera / Q000235:genetics* / Q000382:microbiology
chemical_list: D051034:Inhibitor of Apoptosis Proteins