Research for the mechanisms of continuous infection and demyelination of Theiler's murine encephalomyelitis virus

泰勒氏鼠脑脊髓炎病毒持续感染及脱髓鞘机制研究

• 批准号: 12670609
• 负责人: KIKUCHI Hitoshi
• 金额: $ 2.18万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670609/
• 关键词: Theiler's murine encephalomyelitis virus; Multiple sclerosis; L*; Demyelination; Persistent infection; 脱髄; 持続感染

Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups on the basis of their biological activities. DA and other members of the TO subgroups cause persistent infection in CNS of mice followed by inflammatory demyelination and serve as an experimental model of multiple sclerosis (MS). In contrast, GDVII subgroups produce an acute fatal neuronal disease and kill mice within 7 days. The pathomechanism of persistent infection and demyelination caused by TMEV remain uncertain. Recently, a novel protein called L* that is synthesized by demyelinating strains of TMEV was reported to play an important role in the persistent infection and demyelination. GDVII subgroups do not synthesize this protein. We made mutant GDVII viruses that could synthesize L*. One of them (GDstemL*AUG) could persistently infect in mice but did not cause demyelination. This result suggests that the responsible regions for demyelination and persistent infection are different. We are now making and evaluating chimera constructs between GDstemL*AUG and DA capsids to determine the critical region for demyelination.

Theiler小鼠脑脊髓炎病毒（TMEV）根据其生物学活性分为两个亚组。DA和TO亚组的其他成员引起小鼠CNS中的持续感染，随后是炎性脱髓鞘，并用作多发性硬化症（MS）的实验模型。相比之下，GDVII亚组产生急性致命的神经元疾病，并在7天内杀死小鼠。TMEV引起持续感染和脱髓鞘的病理机制尚不清楚。近年来，TMEV脱髓鞘株合成的一种新蛋白L* 被报道在TMEV持续感染和脱髓鞘过程中发挥重要作用。GDVII亚群不合成这种蛋白质。我们制造了突变的GDVII病毒，可以合成L*。其中一株（GDstemL*AUG）能持续感染小鼠，但不引起脱髓鞘。这一结果表明，脱髓鞘和持续感染的负责区域是不同的。我们现在正在制作和评估GDstemL*AUG和DA衣壳之间的嵌合体构建体，以确定脱髓鞘的关键区域。

项目成果

Kira J, Horiuchi I, Suzuki J, Osoegawa M, Tobimatsu S, Murai H, Minohara M, Furue M, Ochi H: "Myelitis associated with atopic disorders in Japan : a retrospective clinical study of the past 20 years"Intern Med. 40. 613-619 (2001)

Kira J、Horiuchi I、Suzuki J、Osoekawa M、Tobimatsu S、Murai H、Minohara M、Furue M、Ochi H：“日本与特应性疾病相关的脊髓炎：过去 20 年的回顾性临床研究”实习医生。

Kawashima T, Doh-ura K, Kikuchi H, Iwaki T: "Cognitive dysfunction in patients with amyotrophic lateral sclerosis is associated with spherical or crescent-shaped ubiquitinated intraneuronal inclusions in the parahippocampal gyrus and amygdala, but not in

Kawashima T、Doh-ura K、Kikuchi H、Iwaki T：“肌萎缩侧索硬化症患者的认知功能障碍与海马旁回和杏仁核中的球形或新月形泛素化神经元内包涵体有关，但与海马旁回和杏仁核中的球形或新月形泛素化神经元内包涵体有关，但与

小副川学 他: "好酸球性脊髄炎の免疫学的・病理学的検討"神経免疫学. 9. 156-157 (2001)

Manabu Kosoekawa 等：“嗜酸粒细胞性脊髓炎的免疫学和病理学研究”《神经免疫学》9. 156-157 (2001)。

Kawashima T, Furuta A, Doh-ura K, Kikuchi H, Iwaki T.: "Ubiquitin-immunoreactive skein-like inclusions in the neostriatum are not restricted to amyotrophic lateral sclerosis, but rather aging-related structures"Acta Neuropathologica (berl) 2001. 100. 43-4

Kawashima T、Furuta A、Doh-ura K、Kikuchi H、Iwaki T.：“新纹状体中的泛素免疫反应性绞状包含物不限于肌萎缩侧索硬化症，而是与衰老相关的结构”Acta Neuropathologica (berl) 2001

Kawashima T, Furuta A, Doh-ura K, Kikuchi H, Iwaki T: "Ubiquitinimmunoreactive skein-like inclusions in the neostriatum are not restricted to amyotrophic lateral sclerosis, but rather aging-related structures"Acta Neuropathol. 100. 43-49 (2000)

Kawashima T、Furuta A、Doh-ura K、Kikuchi H、Iwaki T：“新纹状体中的泛素免疫反应性绞纱样内含物不仅限于肌萎缩侧索硬化症，而是与衰老相关的结构”Acta Neuropathol。