MOLECULAR BIOLOGY OF HUMAN VIRUS INFECTIONS, HIV-1 AND JCV

进行性多灶性白质脑病（PML）和艾滋病脑病 是病毒引起的神经系统疾病， 处于免疫障碍状态 我们研究了 这些疾病的发病机制，通过开发实验室检测， 检查人类多瘤病毒，JCV作为PML的原因，以及人类 免疫缺陷病毒，HIV- 1，艾滋病。 我们发现人类胎儿 神经胶质细胞和成人B细胞具有共同的DNA蛋白结合因子， 识别JCV DNA的调控序列此外，我们还 证明了在脱髓鞘白色中发现的B细胞中存在JCV。 从PML的情况下的问题。 使用PCR技术，JCV DNA的存在 PML患者的外周血淋巴细胞中有少量淋巴细胞。 这些数据 提示B细胞可能作为JCV的造血载体 神经系统感染。 JCV基因组的鉴定 外周血淋巴细胞中的DNA也在几个艾滋病 没有PML的患者表明JCV可能在 血液在临床神经系统疾病之前。 这些 个体被认为处于发展PML的高风险中。的作用 星形胶质细胞在艾滋病脑病发病机制中的作用 也进行了研究。 人胎脑星形胶质细胞的快速分离 当HIV- 1基因组被转染到细胞中时， 一个短期的生产性感染之后是一个阶段， 持续性病毒感染细胞将重新进入生产阶段， 感染时存在T细胞或细胞因子肿瘤坏死 因子-α和白细胞介素1 β。HIV-1感染的星形胶质细胞也可以 在儿童艾滋病患者的脑组织中被发现。 人类 胎儿星形胶质细胞和雪旺细胞也被证明是易感的， 其它亲神经性人类病毒如水痘-带状疱疹病毒 引起带状疱疹。 这些细胞类型也可以作为病毒的位点， 在初次感染和表现之间的多年潜伏期 神经元感染

Progressive multifocal leukoencephalopathy (PML) and AIDS encephalopathy are virally induced neurological diseases which occur almost exclusively in the setting of a dysimmune state. We have investigated the molecular pathogenesis of these diseases by developing laboratory assays that examine the human polyomavirus, JCV as the cause of PML, and the Human Immunodeficiency Virus, HIV- 1, in AIDS. We have found that human fetal glial and adult B cells have common DNA proteins binding factors which recognize the regulatory sequences of JCV DNA Furthermore, we have also demonstrated the presence of JCV in B cells found in demyelinated white matter from cases of PML. Using PCR technology, the presence of JCV DNA in peripheral blood lymphocytes of PML patients was noted. These data suggest that the B cell may act as a hematogenous vector for JCV infection of the nervous system. The identification of the JCV genome DNA in peripheral blood lymphocytes has also been made in several AIDS patients who do not have PML suggesting that JCV may circulate in the blood prior to the time of clinical neurological disease. These individuals are considered at high risk of developing PML. The role of astroglial cells in the brain in the pathogenesis of AIDS encephalopathy has also been studied. Astrocytes from human fetal brain rapidly transcribe the HIV- 1 genome when it is transfected into cells in culture.A short period of productive infection is followed by a stage of persistent viral infection. The cells will re-enter a productive phase of infection in the presence of T cells or the cytokines tumor necrosis factor-alpha and interleukin l beta. HIV-I infected astrocytes can also be identified in the brain tissue of pediatric AIDS patients. Human fetal astrocytes and Schwann cells have also been shown to be susceptible to other neurotropic human viruses such as varicella-zoster virus which causes shingles. These cell types may also serve as sites of viral latency during the many years between initial infection and demonstration of neuronal infection.