Research on Human Retrovirus as a Pathogenic Agents and its Treatment.

人类逆转录病毒作为致病因子及其治疗的研究。

• 批准号: 08557019
• 负责人: YOSHIKI Takashi
• 金额: $ 6.4万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557019/
• 关键词: HTLV-I; Disease model; Transgenic rat; Apoptosis; HTLV-I; モデル動物; TNFα; トランスジュニック; ラット

Human T lymphocyte virus type I (HTLV-I) is associated with a number of diverse clinical disorders. To investigate the pathogenesis of the HTLV-I related disease, rats carrying HTLV-I (HAM rats) and those transgened with env-pX gene (env-pX rats) were investigated.1) HAM rats develop a chronic progressive myelopathy after long incubation periods. The myelopathy is caused by demyelination based on apoptosis of oligodendrocytes. Microglias were infected with HTLV-I.High expression of pX mRNA and TNF-alpha is observed before apoptosis in the diseased spinal cord, while low of bcl-2.2) env-pX rats develop a wide spectrum of collagen vascular and autoimmune diseases. Peripheral T lymphocytes of these rats express high amount of CD80/86 and ICAM-I showing high response to various antigens. The T lymphocytes infiltrated to the diseased organ/tissu were oligoclonal. Bone marrow transplantation experiments suggest that at least 3 types of pathogenic process are concerned to develop diseases.3) Ick promotor env-pX rats show lymphoid tissue specific expression of pX mRNA.They develop thymomas but not ATL until now.

人类 T 淋巴细胞病毒 I 型 (HTLV-I) 与许多不同的临床疾病有关。为了探讨HTLV-I相关疾病的发病机制，对携带HTLV-I的大鼠（HAM大鼠）和转入env-pX基因的大鼠（env-pX大鼠）进行了研究。 1）HAM大鼠在长时间孵育后出现慢性进行性脊髓病期间。脊髓病是由少突胶质细胞凋亡引起的脱髓鞘引起的。小胶质细胞感染HTLV-I。在患病脊髓凋亡前观察到pX mRNA和TNF-α的高表达，而bcl-2.2) env-pX大鼠的低表达导致多种胶原血管和自身免疫性疾病。这些大鼠的外周T淋巴细胞表达大量CD80/86和ICAM-I，对各种抗原表现出高反应。浸润到病变器官/组织的T淋巴细胞是寡克隆的。骨髓移植实验表明，至少有3种致病过程与疾病的发生有关。3) Ick启动子env-pX大鼠淋巴组织中pX mRNA特异性表达。迄今为止，它们出现胸腺瘤，但尚未出现ATL。

项目成果

Ishizu, A.: "Interleukin-1alpha regulates Thy-1 expression on rat vascular endothelial cells." Microvascul. Res.53. 73-78 (1997)

Ishizu, A.：“Interleukin-1alpha 调节大鼠血管内皮细胞上的 Thy-1 表达。”

Tomaru, U.: "Human T Lymphocyte Virus Type I-Induced Myeloneuropathy in Rats : Implication of Local Activation of the pX and Tumor Necrosis Factor-alpha Genes in Pathogenesis." J.Infect.Dis.174. 318-323 (1996)

Tomaru, U.：“人类 T 淋巴细胞病毒 I 型诱导的大鼠脊髓神经病：pX 和肿瘤坏死因子-α 基因局部激活在发病机制中的意义。”

Ishizu, A.: "Interleukin-1 α regulates Thy-1 expression on rat vascular endothelial cells." Microvascul.Res.53. 73-78 (1997)

Ishizu, A.：“Interleukin-1 α 调节大鼠血管内皮细胞上的 Thy-1 表达。”Microvascul.Res.53 (1997)。

Yoshiki, T.: "Pathology of the diseases caused by human retrovirus" Proc.Jpn.Soc.Pathol.86. 21-45 (1997)

Yoshiki, T.：“人类逆转录病毒引起的疾病的病理学”Proc.Jpn.Soc.Pathol.86。

Kishimoto, T.: "Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo : The importance of surface sialyl Lewis^a antigen." Int J Cancer. 69. 290-294 (1996)

Kishimoto, T.：“与胰腺腺癌体内转移特性相关的表型：表面唾液酸路易斯^a抗原的重要性。”