A protein critical for a Theiler's virus-induced immune system-mediated demyelinating disease has a cell type-specific antiapoptotic effect and a key role in virus persistence
A protein critical for a Theiler's virus-induced immune system-mediated demyelinating disease has a cell type-specific antiapoptotic effect and a key role in virus persistence
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DOI：
10.1128/jvi.72.11.8605-8612.1998
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发表时间：
1998-11-01
影响因子：
5.4
通讯作者：
Roos, RP
中科院分区：
文献类型：
--
作者：
Ghadge, GD;Ma, L;Roos, RP
泰勒氏小鼠脑脊髓炎病毒(TMEV)亚群毒株可引起小鼠持续性中枢神经系统感染和脱髓鞘疾病。本病可作为多发性硬化症(MS)的实验模型，因为这两种疾病都有相似的炎性白质病理，而且因为免疫系统似乎在两个过程中都介导了脱髓鞘，我们先前报道(H.H.Chen，W，P.Wong，L，Zhang，P.L，Ward，and R，P，Roos，NAT，Med，1：927-931,1995)亚群毒株使用另一种起始密码子(除了用于从一个长的开放阅读框架合成微小核糖核酸病毒多蛋白的AUG之外)翻译L，一种新的蛋白质，它与多聚蛋白不在框架内，在脱髓鞘疾病中发挥关键作用。我们现在证明L*在巨噬细胞中具有抗凋亡活性，并且是病毒持续存在的关键。L的抗凋亡作用以及L蛋白和病毒粒子衣壳蛋白的差异翻译可能促进病毒在巨噬细胞中的持续存在，干扰病毒的清除，炎性细胞中细胞凋亡活性的调节可能在TMEV诱导的脱髓鞘疾病和MS的发病机制中起重要作用。
TO subgroup strains of Theiler's murine encephalomyelitis virus (TMEV) induce a persistent central nervous system infection and demyelinating disease in mice. This disease serves as an experimental model of multiple sclerosis (MS) because the two diseases have similar inflammatory white matter pathologies and because the immune system appears to mediate demyelination in both processes, We previously reported (H. H. Chen, W, P. Wong, L, Zhang, P. L, Ward, and R, P, Roos, Nat, Med, 1:927-931, 1995) that TO subgroup strains use an alternative initiation codon (in addition to the AUG used to synthesize the picornavirus polyprotein from one long open reading frame) to translate L*, a novel protein that is out of frame with the polyprotein and which plays a key role in the demyelinating disease. We now demonstrate that L* has antiapoptotic activity in macrophage cells and is critical for virus persistence. The antiapoptotic action of L* as well as the differential translation of L* and virion capsid proteins may foster virus persistence in macrophages and interfere with virus clearance, The regulation of apoptotic activity in inflammatory cells may be important in the pathogenesis of TMEV-induced demyelinating disease as well as MS.