title: The inhibitors of apoptosis of Epiphyas postvittana nucleopolyhedrovirus.
abstract: In this study, four inhibitor of apoptosis genes (iaps) in the genome of Epiphyas postvittana nucleopolyhedrovirus (EppoMNPV) that are homologous to iap-1, iap-2, iap-3 and iap-4 genes of other baculoviruses have been identified. All four iap genes were sequenced and the iap-1 and iap-2 genes were shown to be functional inhibitors of apoptosis. The iap-1, iap-2 and iap-3 genes contain two baculovirus apoptosis inhibitor repeat motifs and a C(3)HC(4) RING finger-like motif. The activity of the iap genes was tested by transient expression in Spodoptera frugiperda (Sf-21) cells treated with the apoptosis-inducing agents actinomycin D, cycloheximide, anisomycin, tumour necrosis factor-alpha and UV light. The iap-2 gene prevented apoptosis induced by all agents tested, indicating activity towards a conserved component(s) of multiple apoptotic pathways. However, the iap-2 gene was unable to function in the absence of a gene immediately upstream of iap-2 that has homology to the orf69 gene of Autographa californica MNPV. The use of a CMV promoter rescued the apoptosis inhibition activity of the iap-2 gene, indicating that the upstream orf69 homologue is associated with expression of iap-2. The iap-1 gene was able to delay the onset of apoptosis caused by all of the induction agents tested but, unlike iap-2, was unable to prevent the development of an apoptotic response upon prolonged exposure of cells to the apoptosis induction agents. No anti-apoptotic activity was observed for the iap-3 and iap-4 genes of EppoMNPV.
authors.affiliation: Department of Microbiology, School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand1.
authors.forename: Terry
authors.initials: T
authors.lastname: Maguire
authors.affiliation: Department of Microbiology, School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand1.
authors.forename: Penelope
authors.initials: P
authors.lastname: Harrison
authors.affiliation: Department of Microbiology, School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand1.
authors.forename: Otto
authors.initials: O
authors.lastname: Hyink
authors.affiliation: Department of Microbiology, School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand1.
authors.forename: James
authors.initials: J
authors.lastname: Kalmakoff
authors.affiliation: Department of Microbiology, School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand1.
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Ward
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D051034:Inhibitor of Apoptosis Proteins; D008969:Molecular Sequence Data; D017924:Nucleopolyhedroviruses / Q000235:genetics*; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus