Chakrabarti L, Hurtrel M, Maire M A, Vazeux R, Dormont D, Montagnier L, Hurtrel B
Unité d'Oncologie Virale, Institut Pasteur, Paris, France.
Am J Pathol. 1991 Dec;139(6):1273-80.
To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express the CD68 marker, suggesting that infected mononuclear phagocytes crossing the blood-brain barrier represent the main source of virus in the CNS. Early viral replication coincided with neuropathologic changes, consisting in gliosis, perivascular infiltrates and rare glial nodules. Immunophenotyping of brain tissue showed that increased macrophage infiltration, microglial reactivity and MHC class II induction occurred within the first week of infection, indicating a possible immunopathologic mechanism in early CNS pathogenesis.
为研究猴免疫缺陷病毒（SIV）进入中枢神经系统（CNS）的机制以及导致神经病理发生的初始事件，在5只恒河猴经静脉接种SIV后7天、1个月、2个月和3个月，通过原位杂交技术对其CNS中的SIV复制情况进行了研究。发现CNS感染是一个常见且早期的事件，因为在所有研究的动物的CNS中均检测到了SIV，且最早在接种后7天就已检测到。在最早阶段，感染主要局限于血管周围细胞。通过联合免疫组织化学和原位杂交技术，发现被感染的细胞表达CD68标志物，这表明穿越血脑屏障的被感染单核吞噬细胞是CNS中病毒的主要来源。早期病毒复制与神经病理变化同时出现，神经病理变化包括胶质增生、血管周围浸润和罕见的胶质结节。脑组织的免疫表型分析显示，在感染的第一周内巨噬细胞浸润增加、小胶质细胞反应性增强以及MHC II类分子诱导增加，这表明在早期CNS发病机制中可能存在免疫病理机制。
