Xing Hui Qin, Moritoyo Takashi, Mori Kazuyasu, Tadakuma Kei, Sugimoto Chie, Ono Fumiko, Hayakawa Hitoshi, Izumo Shuji
Division of Molecular Pathology and Genetic Epidemiology, Center for Chronic Viral Diseases, Kagoshima University, Kagoshima, Japan.
J Neurovirol. 2003 Aug;9(4):508-18. doi: 10.1080/13550280390218904.
Highly active antiretroviral therapy (HAART) has been successful to reduce progression of acquired immunodeficiency syndrome (AIDS). Nevertheless, recent autopsy analysis of the brain from patients with human immunodeficiency virus (HIV)-1 infection reported same or even increasing numbers of AIDS encephalopathy. This insufficient effect of HAART for central nervous system (CNS) complication might be explained by independent pathogenetic processes in lymph node and CNS. We inoculated macaques with three Simian immunodeficiency virus (SIV) strains and investigated relationship between degree of the lymph node pathology and that of AIDS-related brain pathology. Animals infected with T-cell-tropic viruses SIVmac239 and SHIV-RT developed typical AIDS pathology in the lymph node 46 to 156 weeks after infection. The cerebral cortex of these animals showed focal or diffuse gliosis, and electron microscopic analysis demonstrated degenerative changes, such as accumulation of dense lamellar bodies in the dendrites and swelling of astrocytic processes. However, there was no evidence of microglial nodules or multinucleated giant cells in the white mater. The animals infected with macrophage-tropic SIV239env/MERT did not develop lymph node pathology of AIDS in the same or longer period of infection. The white mater of the animal, however, showed microglial nodules with multinucleated giant cells, a pathological hallmark of AIDS encephalopathy. SIV immunoreactivity was demonstrated in these giant cells as well as macrophage/microglia cells. On the other hand, there was no abnormality in the cerebral cortex. These findings suggest that there are two independent pathogenetic processes in AIDS encephalopathy: immune response against virus infected macrophage/microglial cells in the white mater without immunodeficiency and cortical degeneration caused in the late stage of AIDS.
高效抗逆转录病毒疗法（HAART）已成功减少了获得性免疫缺陷综合征（AIDS）的进展。然而，最近对人类免疫缺陷病毒（HIV）-1感染患者大脑进行的尸检分析报告显示，患艾滋病脑病的人数相同甚至有所增加。HAART对中枢神经系统（CNS）并发症的这种效果不佳可能是由淋巴结和中枢神经系统中独立的致病过程所解释的。我们用三种猿猴免疫缺陷病毒（SIV）毒株接种猕猴，并研究淋巴结病理学程度与艾滋病相关脑病理学程度之间的关系。感染嗜T细胞病毒SIVmac239和SHIV-RT的动物在感染后46至156周出现了典型的淋巴结艾滋病病理学变化。这些动物的大脑皮层显示局灶性或弥漫性胶质增生，电子显微镜分析显示有退行性变化，如树突中致密板层小体的积累和星形细胞突起的肿胀。然而，在白质中没有小胶质结节或多核巨细胞的证据。感染嗜巨噬细胞SIV239env/MERT的动物在相同或更长的感染期内未出现艾滋病的淋巴结病理学变化。然而，该动物的白质显示有含多核巨细胞的小胶质结节，这是艾滋病脑病的病理特征。在这些巨细胞以及巨噬细胞/小胶质细胞中证实了SIV免疫反应性。另一方面，大脑皮层没有异常。这些发现表明，艾滋病脑病存在两个独立的致病过程：对白质中病毒感染的巨噬细胞/小胶质细胞的免疫反应而无免疫缺陷，以及艾滋病晚期引起的皮层退化。
