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

为了澄清神经探索的发病机理，使用原位PCR HTLV-I Provirus的双染色和TSP的脊髓病变与疾病的持续时间相关，与疾病的持续时间相关。 TSP患者比Thalthy携带者多，并且与疾病进展率，抗HTLV-I AB滴度以及CSF中的Neopterin。 HAM/TSP PA…使用原位PCR和高度敏感的免疫组织化学技术。 loal loal loal loal loal loal loal loal载荷可减少。我们还研究了htlv-i载体中一种持久性的模式。血液样本对HTLV-I规定为阴性。接受扁桃体切除术和HTLV-I感染细胞的定位显示，仅检测到这种区域HTLV-1中的细胞感染个体。