The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose
The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose
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DOI：
10.1099/vir.0.19447-0
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发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Ng, ML
中科院分区：
文献类型：
--
作者：
Chu, JJH;Ng, ML
西尼罗病毒诱导细胞死亡的机制是由初始感染剂量决定的。WN病毒感染10或以上的Vero细胞，早在感染后8 h （p.i.）就观察到坏死的形态学变化特征。病理改变包括广泛的细胞肿胀和质膜完整性丧失，如光学和电子显微镜所示。胞外乳酸脱氢酶（LDH）活性高，高迁移率组1 （HMGB1）蛋白渗漏到胞外空间。当细胞发生坏死时，它们释放HMGB1蛋白，一种促炎介质细胞因子。在高感染剂量下，细胞质膜完整性的丧失是由于WN子代病毒颗粒在成熟过程中大量出芽。当细胞松弛素B破坏这种丰富的出芽过程时，LDH活性显著降低。相比之下，当细胞感染的m.o.i.小于等于1时，WIN病毒诱导的细胞杀伤主要以凋亡方式发生；细胞凋亡过程在感染后很晚才发生（p.i. 32 h）。DNA断裂，染色质凝集，凋亡小体形成。这种病毒诱导的凋亡途径是由细胞色素c的释放启动的；并伴有凋亡细胞的形成。反过来，这导致caspase-9和-3的激活，并导致聚（adp -核糖）聚合酶的裂解。
The mechanism of West Nile (WN) virus-induced cell death is determined by the initial infectious dose. In Vero cells infected with WN virus at an m.o.i. of 10 or greater, morphological changes characteristic of necrosis were observed as early as 8 h post-infection (p.i.). Pathological changes included extensive cell swelling and loss of plasma membrane integrity, as revealed by optical and electron microscopy. High extracellular lactate dehydrogenase (LDH) activity was observed together with leakage of the high mobility group 1 (HMGB1) protein into the extracellular space. When cells undergo necrosis, they release the HMGB1 protein, a pro-inflammatory mediator cytokine. At high infectious doses, loss of cell plasma membrane integrity was due to the profuse budding of WN progeny virus particles during maturation. When this profuse budding process was disrupted using cytochalasin B, LDH activity was reduced dramatically. In contrast, WIN virus-induced cell killing occurred predominantly by apoptosis when cells were infected with an m.o.i. of less than or equal to1; the process of apoptosis observed was much later after infection (32 h p.i.). Fragmentation of DNA, chromatin condensation and formation of apoptotic bodies were all observed. This WN virus-induced apoptosis pathway was initiated by the release of cytochrome c; from the mitochondria and was accompanied by the formation of apoptosomes. In turn, this led to the activation of caspase-9 and -3, and to the cleavage of the poly(ADP-ribose) polymerase.