Infection kinetics, prostacyclin release and cytokine-mediated modulation of the mechanism of cell death during bluetongue virus infection of cultured ovine and bovine pulmonary artery and lung microvascular endothelial cells.
Bluetongue virus (BTV) infection causes a haemorrhagic disease in sheep, whereas BTV infection typically is asymptomatic in cattle. Injury to the endothelium of small blood vessels is responsible for the manifestations of disease in BTV-infected sheep. The lungs are central to the pathogenesis of BTV infection of ruminants; thus endothelial cells (ECs) cultured from the pulmonary artery and lung microvasculature of sheep and cattle were used to investigate the basis for the disparate expression of bluetongue disease in the two species. Ovine and bovine microvascular ECs infected at low multiplicity with partially purified BTV were equally susceptible to BTV-induced cell death, yet ovine microvascular ECs had a lower incidence of infection and produced significantly less virus than did bovine microvascular ECs. Importantly, the relative proportions of apoptotic and necrotic cells were significantly different in BTV-infected EC cultures depending on the species of EC origin and the presence of inflammatory mediators in the virus inoculum. Furthermore, BTV-infected ovine lung microvascular ECs released markedly less prostacyclin than the other types of ECs. Results of these in vitro studies are consistent with the marked pulmonary oedema and microvascular thrombosis that characterize bluetongue disease of sheep but which rarely, if ever, occur in BTV-infected cattle.
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA1.
Christopher D
CD
DeMaula
Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 59717, USA2.
Mark A
MA
Jutila
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA1.
Dennis W
DW
Wilson
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA1.
N James
NJ
MacLachlan
D000818:Animals; D017209:Apoptosis; D001820:Bluetongue virus / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology*; D011464:Epoprostenol / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000821:virology*; D012756:Sheep
D016207:Cytokines; D018836:Inflammation Mediators; D011464:Epoprostenol