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

为了阐明由慢性病毒感染引起的神经疾病的发病机理，我们首先研究了HTLV-1感染细胞在HAM/TSP中使用原位PCR进行HTLV-I Provirus和细胞表面标志物的免疫组织化学的定位。 HTLV-I前病毒DNA位于浸润的UCHL-1+ T细胞中，尤其是在血管周围区域。 HTLV-I+细胞的数量与疾病活性正相关，并与疾病持续时间负相关。此外，使用Taqman PCR方法，通过定量PCR测量了202名HAM/TSP患者和206 HTLV-I载体外周血单核细胞的前尿负荷。 HAM/TSP患者的临时负荷远高于健康携带者的临时负荷，并且与疾病进展率，抗HTLV-I AB滴度和值相关。在CSF中，新近临时载荷和经常税收蛋白表达在HAM/TSP PA的PBMC和CSF细胞中也证明了更多的提示……更多提示使用原位PCR和高度敏感的免疫组织化学技术。综上所述，这些发现表明，其抗原的HTLV-I临时负荷和表达在HAM/TSP的致病机制中很重要，并且是减少病毒载量的治疗方法，并且其表达可能适用于HAM/TSP的治疗。我们还研究了HTLV-I携带者中一种持久感染的模式。在从纵向系列患者中收集的500个血液样本中，所有HTLV-I血清阳性样品均为PCR检测HTLV-I Provirus阳性，HTLV-I血清阴性血液样本均为HTLV-I Profirus阴性。这表明血清阴性HTLV-I载体很少见，并且在HTLV-I感染中可能不经常受到血清阴性血donner的感染。从接受扁桃体切除术并检查HTLV-I感染细胞的定位的一系列患者中收集了100吨扁桃体。 HTLV-I血清阳性患者的所有扁桃体均显示边缘区域和HTLV-1病毒的面积增加，仅在此类区域中检测到。这些发现表明，扁桃体可能是持续感染的部位，并且是HTLV-I感染个体中受感染细胞的参与者。较少的