Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis

• Published in: Journal of general virology Vol. 91; no. Pt 4; pp. 1038 - 1046
• Main Authors: Johns, H.L, Bensaude, E, La Rocca, S.A, Seago, J, Charleston, B, Steinbach, F, Drew, T.W, Crooke, H, Everett, H
• Format: Journal Article
• Language: English
• Published: England 01.04.2010
• Subjects: Animals; aorta; Aorta - drug effects; Aorta - pathology; Aorta - virology; apoptosis; Apoptosis - drug effects; BH3 Interacting Domain Death Agonist Protein - physiology; Caspases - metabolism; Cells, Cultured; Classical swine fever virus; Classical Swine Fever Virus - pathogenicity; Cytochromes c - metabolism; endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Endothelial Cells - virology; endothelium; Enzyme Activation; host-pathogen relationships; infection; oligonucleotides; pathogenesis; pIpC oligonucleotide; RNA, Double-Stranded - pharmacology; Swine; Viral Envelope Proteins - physiology; virus replication
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.016576-0

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 Npro and Erns 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.