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MOLECULAR PATHOLOGICAL ANALYSIS OF NERVOUS DISEASES CAUSED BY CHRONIC VIRAL INFECTION

慢性病毒感染引起的神经疾病的分子病理学分析

基本信息

批准号：
08457193
负责人：
IZUMO Shuji
金额：
$ 4.74万
依托单位：
KAGOSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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-08457193/
关键词：
HTLV-I HAM in situ PCR proviral load persistent infection immunohistochemistry molecular pathology HTLV-I ウイルス

项目摘要

In order to clarify pathogenesis of the nervous diseases caused by chronic viral infection, we firstly investigated localization of HTLV-I infected cells in the spinal cord lesion of HAM/TSP using double staining of in situ PCR for HTLV-I provirus and immunohistochemistry of cell surface markers. HTLV-I proviral DNA was localized at infiltrated UCHL-1+ T-cells especially in the perivascular areas. Numbers of HTLV-I+ cells were positively correlated with the disease activity and negatively with duration of illness. In addition, proviral loads of peripheral blood mononuclear cells in 202 HAM/TSP patients and 206 HTLV-I carriers were measured by quantitative PCR using TaqMan PCR method. The proviral load of HAM/TSP patients was much higher than that of healthy carrier and correlated with the disease progression rate, anti-HTLV-I Ab titers, and the values of. neopterin in CSF.A high proviral load and frequent Tax protein expression were also demonstrated in PBMC and CSF cells of HAM/TSP pa … More tients using in situ PCR and highly sensitive immunohistochemistry technique. Taken together, these findings suggested that HTLV-I proviral load and expression of its antigens are important in pathogenic mechanism of HAM/TSP and a therapeutic method to reduce viral load and its expression may be suitable for the treatment of HAM/TSP.We also investigated a mode of persistent infection in HTLV-I carriers. Among 500 blood samples collected from a longitudinal series of patients, all HTLV-I sero-positive samples were positive for PCR detection of HTLV-I provirus and all of HTLV-I sero-negative blood samples were negative for HTLV-I provirus. This suggested that sero-negative HTLV-I carrier is rare and infection from a sero-negative blood donner may not be frequent in HTLV-I infection. Totally 100 tonsils were collected from a series of patients who received tonsillectomy and examined localization of HTLV-I infected cells. All tonsils from HTLV-I sero-positive patients showed increased area of marginal zone and HTLV-I provirus was detected only from such areas. These findings suggested a possibility that the tonsil might be a site of persistent infection and a reservoir of infected cells in HTLV-I infected individuals. Less

为阐明慢性病毒感染所致神经系统疾病的发病机制，本研究首次采用HTLV-I原病毒原位PCR和细胞表面标志物免疫组化双重染色技术，对HAM/TSP脊髓病变中HTLV-I感染细胞的定位进行了研究。HTLV-I前病毒DNA定位于浸润的UCHL-1+ T细胞，特别是在血管周围区域。HTLV-I+细胞数与疾病活动性呈正相关，与病程呈负相关。同时采用TaqMan PCR方法对202例HAM/TSP患者和206例HTLV-Ⅰ携带者外周血单个核细胞前病毒载量进行定量检测。HAM/TSP患者的前病毒载量明显高于健康携带者，并与疾病进展率、抗HTLV-Ⅰ抗体滴度、HAM/TSP患者PBMC和CSF细胞中也存在高的前病毒载量和频繁的Tax蛋白表达， ...更多信息采用原位PCR和高灵敏度免疫组化技术对10例正常人进行了检测。以上结果提示HTLV-Ⅰ前病毒载量及其抗原表达在HAM/TSP的发病机制中起重要作用，降低病毒载量及其抗原表达的治疗方法可能适用于HAM/TSP的治疗。在从纵向系列患者收集的500份血液样品中，所有HTLV-I血清阳性样品对HTLV-I前病毒的PCR检测均为阳性，所有HTLV-I血清阴性血液样品对HTLV-I前病毒均为阴性。这表明血清阴性HTLV-Ⅰ携带者是罕见的，来自血清阴性献血者的感染在HTLV-Ⅰ感染中可能不常见。从接受扁桃体切除术的一系列患者中收集总共100个扁桃体，并检查HTLV-I感染细胞的定位。所有HTLV-Ⅰ血清阳性患者的扁桃体边缘区面积增加，仅在这些区域检测到HTLV-Ⅰ前病毒。这些发现表明，扁桃体可能是一个持续感染的网站和受感染的细胞在HTLV-I感染的个人水库的可能性。少