title: Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells.
abstract: Infection with virulent strains of classical swine fever virus (CSFV) results in an acute haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopenia and immunosuppression, whereas for less virulent isolates infection can become chronic. In view of the haemorrhagic pathology of the disease, the effects of the virus on vascular endothelial cells was studied by using relative quantitative PCR and ELISA. Following infection, there was an initial and short-lived increase in the transcript levels of the proinflammatory cytokines interleukins 1, 6 and 8 at 3 h followed by a second more sustained increase 24 h post-infection. Transcription levels for the coagulation factor, tissue factor and vascular endothelial cell growth factor involved in endothelial cell permeability were also increased. Increases in these factors correlated with activation of the transcription factor NF-kappaB. Interestingly, the virus produced a chronic infection of endothelial cells and infected cells were unable to produce type I interferon. Infected cells were also protected from apoptosis induced by synthetic ouble-stranded RNA. These results demonstrate that, in common with the related pestivirus bovine viral diarrhoea virus, CSFV can actively block anti-viral and apoptotic responses and this may contribute to virus persistence. They also point to a central role for infection of vascular endothelial cells during the pathogenesis of the disease, where a proinflammatory and procoagulant endothelium induced by the virus may disrupt the haemostatic balance and lead to the coagulation and thrombosis seen in acute disease.
authors.affiliation: Department of Virology, Veterinary Laboratories Agency, Weybridge, Surrey KT15 3NB, UK.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bensaude
authors.affiliation: Department of Virology, Veterinary Laboratories Agency, Weybridge, Surrey KT15 3NB, UK.
authors.forename: Jane L E
authors.initials: JLE
authors.lastname: Turner
authors.affiliation: Department of Virology, Veterinary Laboratories Agency, Weybridge, Surrey KT15 3NB, UK.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Wakeley
authors.affiliation: Department of Immunology and Pathology, BBSRC Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Sweetman
authors.affiliation: Department of Immunology and Pathology, BBSRC Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Pardieu
authors.affiliation: Department of Virology, Veterinary Laboratories Agency, Weybridge, Surrey KT15 3NB, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Drew
authors.affiliation: Department of Immunology and Pathology, BBSRC Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wileman
authors.affiliation: Department of Immunology and Pathology, BBSRC Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, UK.
authors.forename: Penelope P
authors.initials: PP
authors.lastname: Powell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002478:Cells, Cultured; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000821:virology; D018836:Inflammation Mediators / Q000378:metabolism; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa; D013925:Thromboplastin / Q000235:genetics*; D014774:Virulence
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D007372:Interferons; D013925:Thromboplastin