AFRICAN HORSE SICKNESS VIRUS INDUCES THE INTRINSIC APOPTOSIS PATHWAY IN CULTURED MAMMALIAN CELLS

摘要

African horse sickness virus (AHSV) belongs to the family Reoviridae under the genus Orbivirus. The virus is the causative agent of African horse sickness (AHS), a highly infectious and economically important disease of the Equidae, and is transmitted to its vertebrate hosts by species of Culicoides (biting midge). Although AHSV replicates in both vertebrate and insect host cells, cytopathic effects are observed only in mammalian cells, resulting in rapid cell death. This type of differential host response has been seen for other arboviruses, including bluetongue virus and has been attributed to the induction of apoptosis. Apoptosis is a physiological process of controlled cell suicide in response to a variety of stimuli and a common pathway of virus-induced cell death. Elimination of infected cells by apoptosis is considered a defense mechanism in multicellular organisms for controlling virus infectionand contributes directly to the cytopathogenesis of these viruses. There are two major pathways of apoptotic cell death induction, namely extrinsic signaling through death receptors and intrinsic signaling mainly through mitochondria. In the intrinsic pathway the loss of mitochondrial transmembrane potential results in the release of cytochrome C from the mitochondrial intermembrane space to the cytosol. Cytochrome C subsequently forms an apoptosome complex that activates a caspase cascade that executes the apoptosis process through the proteolytic cleavage of a number of intracellular substrates. Ultimately, apoptotic cells are fragmented into apoptotic bodies which are rapidly phagocytosed by neighboring cells, thereby preventing inflammation, as well as limiting virus replication and spread. Whether the pathogenesis caused by AHSV in mammalian cells is due to the induction of apoptosis is as yet unclear. The aim of this study was to assess whether AHSV induces apoptosis in cultured mammalian cells.