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[蓝舌病毒感染:细胞凋亡过程中激活的信号通路]

[Bluetongue virus infection: signaling pathway activated during apoptosis].

作者信息

Mortola E, Larsen A

机构信息

Inmunología Veterinaria, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, (1900) La Plata, Argentina.

出版信息

Rev Argent Microbiol. 2009 Jun-Sep;41(3):134-40.

Abstract

Bluetongue (BTV) is a double-stranded RNA virus that induces apoptosis both in mammalian cell cultures and in target tissues. To elucidate the apoptosis pathways in BTV infection, we have examined in detail the apoptosis mechanism by examination of caspases, Bax, cytochrome c, Smac/DIABLO and NF-B signalling pathways. In this report, after cell infection with BTV, the activation of caspase 8 was detected, proving the extrinsic receptor binding apoptotic pathway. Apoptosis followed a sequential pathway involving the detection of activated Bcl-2 family members. Furthermore, its translocation to the mitochondria, as well as the release of cytochrome c and Smac/Diablo confirmed that BTV apoptosis involves the sequential intrinsic pathway. In addition, we demonstrated that NF-kappaB was activated following BTV infection and cell treatment with an inhibitor peptide before BTV infection, prevented NF-kappaB activation and substantially reduced cellular apoptosis. Our accumulating data concerning the activation of Bax, cytochrome c, Smac/DIABLO and NF-kappaB clarify the mechanism of apoptosis during BTV infection, and confer a better understanding of the primary role of apoptosis in BTV pathogenesis.

摘要

蓝舌病病毒(BTV)是一种双链RNA病毒,可在哺乳动物细胞培养物和靶组织中诱导细胞凋亡。为了阐明BTV感染中的凋亡途径,我们通过检测半胱天冬酶、Bax、细胞色素c、Smac/DIABLO和NF-κB信号通路,详细研究了凋亡机制。在本报告中,细胞感染BTV后,检测到半胱天冬酶8的激活,证明了外源性受体结合凋亡途径。凋亡遵循一个涉及检测活化的Bcl-2家族成员的顺序途径。此外,其向线粒体的转位以及细胞色素c和Smac/Diablo的释放证实,BTV凋亡涉及顺序性的内源性途径。此外,我们证明BTV感染后NF-κB被激活,并且在BTV感染前用抑制剂肽处理细胞可阻止NF-κB激活并显著减少细胞凋亡。我们关于Bax、细胞色素c、Smac/DIABLO和NF-κB激活的累积数据阐明了BTV感染期间的凋亡机制,并有助于更好地理解凋亡在BTV发病机制中的主要作用。

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