title: Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis.
abstract: Classical swine fever virus (CSFV) causes severe disease in pigs associated with leukopenia, haemorrhage and fever. We show that CSFV infection protects endothelial cells from apoptosis induced by the dsRNA mimic, pIpC, but not from other apoptotic stimuli, FasL or staurosporine. CSFV infection inhibits pIpC-induced caspase activation, mitochondrial membrane potential loss and cytochrome c release as well as the pro-apoptotic effects of truncated Bid (tBid) overexpression. The CSFV proteins N(pro) and E(rns) both contribute to CSFV inhibition of apoptosis. We conclude that CSFV infection can inhibit apoptotic signalling at multiple levels, including at the caspase-8 and the mitochondrial checkpoints. By supporting viral replication, endothelial cells may promote CSFV pathogenesis.
authors.affiliation: Virology Department, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Johns
authors.forename: E
authors.initials: E
authors.lastname: Bensaude
authors.forename: S A
authors.initials: SA
authors.lastname: La Rocca
authors.forename: J
authors.initials: J
authors.lastname: Seago
authors.forename: B
authors.initials: B
authors.lastname: Charleston
authors.forename: F
authors.initials: F
authors.lastname: Steinbach
authors.forename: T W
authors.initials: TW
authors.lastname: Drew
authors.forename: H
authors.initials: H
authors.lastname: Crooke
authors.forename: H
authors.initials: H
authors.lastname: Everett
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000821:virology; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D006692:Classical Swine Fever Virus / Q000472:pathogenicity*; D045304:Cytochromes c / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D004789:Enzyme Activation; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D013552:Swine; D014759:Viral Envelope Proteins / Q000502:physiology
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D012330:RNA, Double-Stranded; D014759:Viral Envelope Proteins; D045304:Cytochromes c; D020169:Caspases