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

进行性多灶性白质脑病与艾滋病脑病 是病毒引起的神经系统疾病，几乎只发生在 在一个动态的国家的背景下。我们已经研究了分子 这些疾病的发病机制是通过发展实验室检测来实现的 检查人类多瘤病毒，JCV作为PML的原因，以及人类 艾滋病中的免疫缺陷病毒，HIV-1。我们发现人类胎儿 胶质细胞和成体B细胞有共同的DNA蛋白结合因子， 识别JCV DNA的调控序列此外，我们还 在脱髓鞘白质中发现B细胞中存在JCV 来自PML病例的物质。用聚合酶链式反应技术检测JCV DNA的存在 在PML患者外周血中发现有淋巴细胞。这些数据 提示B细胞可作为JCV的血源性载体 神经系统的感染。日本血吸虫基因组的鉴定 外周血淋巴细胞中的DNA也在几种艾滋病患者中产生 没有PML的患者提示JCV可能在 血液在临床神经系统疾病前的时间。这些 个人被认为是患PML的高危人群。的作用 脑内星形胶质细胞在艾滋病脑病发病中的作用 也被研究过。快速从人胎脑中提取星形胶质细胞 当HIV-1基因组被转染到细胞中时转录它 文化。在短暂的生产性感染之后，会有一个阶段 持续的病毒感染。细胞将重新进入生产阶段 感染时存在T细胞或细胞因子的肿瘤坏死 因子-α和白介素β-L。感染HIV-I的星形胶质细胞也可以 在儿童艾滋病患者的脑组织中被鉴定。人类 胎儿星形胶质细胞和雪旺细胞也被证明是易感细胞。 对其他嗜神经性人类病毒，如水痘带状疱疹病毒 导致带状疱疹。这些细胞类型也可能是病毒感染的场所。 从最初感染到发病之间的多年潜伏期 神经感染的症状。

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.