tailieunhanh - Báo cáo y học: " Role of cellular caspases, nuclear factor-kappa B and interferon regulatory factors in Bluetongue virus infection and cell fate"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Role of cellular caspases, nuclear factor-kappa B and interferon regulatory factors in Bluetongue virus infection and cell fate | Stewart and Roy Virology Journal 2010 7 362 http content 7 1 362 VIROLOGY JOURNAL RESEARCH Open Access Role of cellular caspases nuclear factor-kappa B and interferon regulatory factors in Bluetongue virus infection and cell fate Meredith E Stewart Polly Roy Abstract Background Bluetongue virus BTV infection causes haemorrhagic disease in ruminants and induces cell death. The pathogenesis in animals and in cell culture has been linked to BTV-induced apoptosis. Results In this report we investigated BTV-induced apoptosis in cell culture in depth and show that both extrinsic caspase-8 activation and intrinsic caspase-9 activation pathways play roles in BTV apoptosis. Further by using chemical inhibitors and knock-out cell lines we show that these pathways act independently of each other in BTV infected cells. In addition to activation of caspase-8 -9 and executioner caspase-3 we also identified that BTV infection causes the activation of caspase-7 which results in the cleavage of poly ADP-ribose polymerase PARP . BTV-induced cell death appears to be due to apoptosis rather than necrosis as the HMBG-1 was not translocated from the nucleus. We also examined if NF-kB response is related to BTV-induced apoptosis as in reovirus. Our data suggests that NF-kB response is not linked to the induction of apoptosis. It is controlled by the degradation of only IftBa but not IwBp resulting in a rapid transient response during BTV infection. This was supported using an NF-kB dependent luciferase reporter gene assay which demonstrated early response that appeared to be suppressed by the late stage of BTV replication. Furthermore virus titres were higher in the presence of NF-kB inhibitor SN50 indicating that NF-kB has a role in initiating an antiviral environment. In addition we show that BTV infection induces the translocation of interferon regulatory factors IRF-3 and IRF-7 into the nucleus. The induction of IRF responses when measured by IRF dependent .

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