Virus tropism, distribution, persistence and pathology in the corpus callosum of the Semliki Forest virus-infected mouse brain: a novel system to study virus-oligodendrocyte interactions
Virus tropism, distribution, persistence and pathology in the corpus callosum of the Semliki Forest virus-infected mouse brain: a novel system to study virus-oligodendrocyte interactions
复制标题
DOI：
10.1111/j.1365-2990.2006.00739.x
复制
发表时间：
2006-08-01
影响因子：
5
通讯作者：
Graham, A.
中科院分区：
文献类型：
--
作者：
Fazakerley, J. K.;Cotterill, C. L.;Graham, A.
病毒感染的少突胶质细胞在体内的细胞病理学的时间过程还没有很好的定义。在这里，我们研究这些事件在小鼠大脑中使用一种新的系统，其中大量的少突胶质细胞可以重复感染。在小鼠中，神经内接种后，甲病毒Semliki Forest病毒（SFV）的A7（74）毒株具有有效的神经侵袭性，中枢神经系统（CNS）感染主要导致免疫介导的脱髓鞘血管周围病变。该研究表明，直接脑内接种SFV A7（74）或SFV 1载体导致脑的主要白色物质束（胼胝体）的显著、选择性和广泛感染。成熟的少突胶质细胞是感染的主要细胞类型。后续事件复杂;早期病毒诱导的感染细胞坏死死亡，随后是邻近明显未感染细胞的凋亡死亡。从第10天开始，明显出现强烈的炎症反应和相当大的髓鞘损失，此后未观察到病毒阳性细胞。相比之下，在无胸腺nu/nu小鼠中，在不存在T细胞应答的情况下，未观察到炎性浸润，并且病毒感染的细胞持续超过30天，具有广泛的空泡化，但脱髓鞘较少。少突胶质细胞从早期破坏性感染到潜在持续性感染的变化可能反映了先天免疫应答的激活。激活外周先天性防御接种聚I：C之前，中枢神经系统病毒感染废除广泛的胼胝体感染。胼胝体的这种广泛感染为研究病毒-少突胶质细胞相互作用提供了一种新的体内系统。
The temporal course of cellular pathology in virus-infected oligodendrocytes in vivo is not well defined. Here we study these events in the mouse brain using a novel system in which large numbers of oligodendrocytes can be reproducibly infected. In the mouse, following extraneural inoculation, the A7(74) strain of the alphavirus Semliki Forest virus (SFV) is efficiently neuroinvasive and central nervous system (CNS) infection leads to predominantly perivascular lesions of immune-mediated demyelination. This study demonstrates that direct intracerebral inoculation with SFV A7(74) or the SFV1 vector results in dramatic, selective and widespread infection of the major white matter tract of the brain, the corpus callosum. Mature oligodendrocytes are the predominant cell type infected. Subsequent events are complex; early virus-induced necrotic death of infected cells is followed by apoptotic death of adjacent apparently uninfected cells. A strong inflammatory response and considerable myelin loss are evident from 10 days and virus-positive cells are not observed after this time. In contrast, in athymic nu/nu mice, in the absence of T-cell responses, no inflammatory infiltrates are observed and virus-infected cells persist for over 30 days with extensive vacuolation but less demyelination. The change from an early destructive to a potentially persistent infection of oligodendrocytes is likely to reflect activation of innate immune responses. Activation of peripheral innate defences by inoculation of poly I : C prior to CNS virus infection abrogates the widespread corpus callosum infection. This widespread infection of the corpus callosum provides a novel in vivo system in which to study virus-oligodendrocyte interactions.