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, wh ereas BTV infection typically is asymptomatic in cattle. Injury to the endo thelium of small blood vessels is responsible for the manifestations of dis ease in BTV-infected sheep. The lungs are central to the pathogenesis of BT V infection of ruminants; thus endothelial cells (ECs) cultured from the pu lmonary artery and lung microvasculature of sheep and cattle were used to i nvestigate the basis for the disparate expression of bluetongue disease in the two species. Ovine and bovine microvascular ECs infected at low multipl icity with partially purified BTV were equally susceptible to BTV-induced c ell death, yet ovine microvascular ECs had a lower incidence of infection a nd produced significantly less virus than did bovine microvascular ECs, Imp ortantly, the relative proportions of apoptotic and necrotic cells were sig nificantly different in BTV-infected EC cultures depending on the species o f EC origin and the presence of inflammatory mediators in the virus inoculu m. Furthermore, BTV-infected ovine lung microvascular ECs released markedly less prostacyclin than the other types of ECs. Results of these in vitro s tudies are consistent with the marked pulmonary oedema and microvascular th rombosis that characterize bluetongue disease of sheep but which rarely, if ever, occur in BTV-infected cattle.