Caspase-3 activation is required for reovirus-induced encephalitis in vivo.
Caspase-3 activation is required for reovirus-induced encephalitis in vivo.
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DOI：
10.3109/13550284.2010.499890
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发表时间：
2010-07
影响因子：
3.2
通讯作者：
Tyler KL
中科院分区：
文献类型：
--
作者：
Beckham JD;Tuttle KD;Tyler KL
新生小鼠呼肠孤病毒感染为了解中枢神经系统（CNS）病毒感染的分子发病机制提供了一个经典的实验系统。许多人类嗜神经病毒（包括疱疹病毒和西尼罗河病毒）引起的中枢神经系统组织损伤与caspase依赖性凋亡神经元细胞死亡有关。我们之前已经证明呼肠孤病毒诱导的中枢神经系统组织损伤是由细胞凋亡引起的，并且与死亡受体和线粒体凋亡途径的激活有关，最终导致下游效应物caspase-3的激活。为了直接研究caspase-3在脑炎期间病毒诱导的神经元死亡和中枢神经系统组织损伤中的作用，我们比较了缺乏caspase-3基因的小鼠（caspase-3(- / -)）和同基因野生型小鼠呼肠孤病毒感染中枢神经系统的发病机制。先前对呼肠孤病毒感染小鼠的抗凋亡治疗的研究表明，对呼肠孤病毒诱导的神经元损伤的保护可以在不改变感染小鼠大脑中的病毒滴度的情况下发生。我们现在表明，呼肠孤病毒感染caspase-3（- / -）小鼠与中枢神经系统组织损伤严重程度的显著降低、大脑中病毒抗原和滴度的降低以及感染小鼠的存活率提高有关。在脑内接种后，作者还表明病毒在呼肠孤病毒感染的caspase-3（- / -）小鼠中从大脑传播到眼睛，这表明病毒在这些小鼠中的传播是完整的。对呼肠孤病毒感染后长期存活的caspase-3（- / -）小鼠的大脑检查显示，这些小鼠最终清除了CNS病毒感染，并且没有表现出残留或延迟的CNS组织损伤。
Reovirus infection of neonatal mice provides a classic experimental system for understanding the molecular pathogenesis of central nervous system (CNS) viral infection. CNS tissue injury, caused by many human neurotropic viruses, including herpes viruses and West Nile virus, is associated with caspase-dependent apoptotic neuronal cell death. We have previously shown that reovirus-induced CNS tissue injury results from apoptosis and is associated with activation of both death-receptor and mitochondrial apoptotic pathways culminating in the activation of the downstream effector caspase, caspase-3. In order to directly investigate the role of caspase-3 in virus-induced neuronal death and CNS tissue injury during encephalitis, we have compared the pathogenesis of reovirus CNS infection in mice lacking the caspase-3 gene (caspase-3 (–/–)) to syngeneic wild-type mice. Prior studies of antiapoptotic treatments for reovirus-infected mice have indicated that protection from reovirus-induced neuronal injury can occur without altering the viral titer in the brains of infected mice. We now show that reovirus infection of caspase-3(–/–) mice was associated with dramatic reduction in severity of CNS tissue injury, decreased viral antigen and titer in the brain, and enhanced survival of infected mice. Following intracerebral inoculation, the authors also show that virus spread from the brain to the eyes in reovirus-infected caspase-3 (–/–) mice, indicating that viral spread was intact in these mice. Examination of brains of long-term survivors of reovirus infection among caspase-3 (–/–) mice showed that these mice eventually clear their CNS viral infection, and do not manifest residual or delayed CNS tissue injury.
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影响因子：
120.7
作者：
Sejvar, JJ;Haddad, MB;Petersen, LR
通讯作者：
Petersen, LR
抑制细胞凋亡可防止西尼罗河病毒诱导的细胞死亡。
影响因子：
4.2
作者：
Kleinschmidt, Malte C.;Michaelis, Martin;Ogbomo, Henry;Doerr, Hans-Wilhelm;Cinatl, Jindrich, Jr.
通讯作者：
Cinatl, Jindrich, Jr.
影响因子：
5.4
作者：
Samuel, Melanie A.;Morrey, John D.;Diamond, Michael S.
通讯作者：
Diamond, Michael S.
影响因子：
64.5
作者：
Graham, Rona K.;Deng, Yu;Hayden, Michael R.
通讯作者：
Hayden, Michael R.
影响因子：
5.4
作者：
Beckham, J. David;Goody, Robin J.;Tyler, Kenneth L.
通讯作者：
Tyler, Kenneth L.