The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis
The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis
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DOI：
10.1038/labinvest.2011.145
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发表时间：
2012-01-01
影响因子：
5
通讯作者：
Doerner, Andrea
中科院分区：
文献类型：
--
作者：
Ebermann, Linda;Wika, Sylwia;Doerner, Andrea
耐药性 C57BL/6 小鼠和宽容型 A.SW/SnJ 小鼠在柯萨奇病毒 B3 (CVB3) 消除方面的明确差异，为研究心肌病毒消除背景下线粒体呼吸链 (RC)、抗氧化应激成分和线粒体相关细胞凋亡之间联系的重要性提供了合适的模型。 C57BL/6 (2.5 +/- 1.4 x 10(4) 斑块形成单位 (p.f.u.)/g 组织) 和 A. SW/SnJ 小鼠 (1.4 +/- 0.8 x 10(7) p.f.u./g) 中不同的心肌 CVB3 滴度与感染后 8 天 (p.i.) 心脏线粒体功能的差异相关。受感染的 C57BL/6 小鼠心脏显示复合物 I (CI) 和 CIII 活性增加，但 RC 的 CII 和正常 CIV 活性受到限制。抗氧化过氧化氢酶表达的减少伴随着脂质过氧化（LPO）的升高，表明氧化应激。 Bax、Bcl-2、caspase 3 水平升高和 DNA 降解表明内在细胞凋亡被激活。相比之下，CVB3 感染的 A.SW/SnJ 小鼠中所有心肌 RC 复合体活动均受到限制。抗氧化系统提供了足够的保护，防止氧化应激，表现为过氧化氢酶表达升高和 LPO 未改变。 CVB3 感染的 A.SW/SnJ 小鼠中 Bax 和 Bcl-2 水平没有变化，而 caspase 3 适度增加，但未检测到 DNA 降解。包括来自两种小鼠品系的数据在内的相关分析表明，CVB3 滴度降低与急性心肌炎 (MC) 期间 CI 和 CIII 活性增加、氧化应激以及活跃细胞凋亡相关。 C57BL/6 小鼠完全消除了 CVB3 和炎症并使所有细胞内参数正常化，而 A. SW/SnJ 小鼠在慢性 MC 90 天注射后表现出永久受限的 CI 活性，此时复制的病毒不再可检测到，但免疫过程仍然活跃。因此，能量代谢的调节对于有效消除病毒至关重要，并且可能对病毒诱导的 MC 患者具有预后和治疗意义。实验室调查 (2012) 92, 125-134; doi：10.1038/labinvest.2011.145； 2011 年 10 月 3 日在线发布
Well-established differences in Coxsackievirus B3 (CVB3) elimination in resistant C57BL/6 and permissive A.SW/SnJ mice provide suitable models for studying the significance of the link between mitochondrial respiratory chain (RC), antioxidative stress components and mitochondrion-related apoptosis in the context of myocardial virus elimination. Distinct myocardial CVB3 titer in C57BL/6 (2.5 +/- 1.4 x 10(4) plaque-forming units (p.f.u.)/g tissue) and A. SW/SnJ mice (1.4 +/- 0.8 x 10(7) p.f.u./g) were associated with differences in the cardiac mitochondrial function 8 days post infection (p.i.). Infected C57BL/6 mouse hearts disclosed increased complex I (CI) and CIII activity, but restricted CII and normal CIV activity of RC. Reduced expression of the antioxidative catalase was accompanied by elevated lipid peroxidation (LPO), indicating oxidative stress. Intrinsic apoptosis was activated demonstrated by elevated levels of Bax, Bcl-2, caspase 3 and DNA degradation. In contrast, all myocardial RC complex activities were restricted in CVB3-infected A. SW/SnJ mice. The antioxidative system provided sufficient protection against oxidative stress shown by an elevated catalase expression and unaltered LPO. Bax and Bcl-2 levels were unchanged in CVB3-infected A. SW/SnJ mice, while caspase 3 was moderately increased but no DNA degradation was detectable. Correlation analyses including data from the two mouse strains revealed that reduced CVB3 titer correlated with increased CI and CIII activity, oxidative stress as well as active apoptosis during acute myocarditis (MC). C57BL/6 mice completely eliminated CVB3 and inflammation and normalized all intracellular parameters, while A. SW/SnJ mice showed permanently restricted CI activity in chronic MC 90 days p.i., at which time the replicating virus was no longer detectable but immunological processes were still active. Consequently, the regulation of energy metabolism appears crucial for an effective virus elimination and may be of prognostic and therapeutic significance for patients with virus-induced MC. Laboratory Investigation (2012) 92, 125-134; doi:10.1038/labinvest.2011.145; published online 3 October 2011