Philippon V, Vellutini C, Gambarelli D, Harkiss G, Arbuthnott G, Metzger D, Roubin R, Filippi P
Laboratoire de virologie, INSERM U 372, Marseille, France.
Virology. 1994 Dec;205(2):519-29. doi: 10.1006/viro.1994.1673.
The HIV and visna lentiviruses induce an inflammatory reaction in the central nervous system (CNS) of the infected hosts leading to dysmyelination, demyelination, and neuronal loss. The basic domain of the transactivating Tat protein has been involved in CNS damage. Infusion of basic containing domain Tat peptides in the lateral ventricle (systemic injection) or in the grey matter, i.e., hippocampus and thalamus (local injection), induced an inflammatory process characterized by the formation of an edema and invasion of macrophage accompanied by reactive astrogliosis. Control peptides originating from either lentiviral proteins or irrelevant protein as ovalbumin did not lead to any inflammatory reaction or cell death. The inflammation led to the loss of ependymal cells in the lateral ventricles and neurons in the grey matter. RNA extracted from the Tat-injected hemisphere reacted with TNF-alpha, IL-1 alpha and beta, and IL-6 probes. The macrophage/microglia inducible nitric oxyde synthase was also expressed. Blockade of TNF-alpha by a pentoxifylline treatment led to the decrease of IL-1 and iNOS expression accompanied by a reduction of the volume of the lesions indicating that the Tat-induced lesions might be mediated by TNF production.
人类免疫缺陷病毒（HIV）和维斯纳慢病毒可在受感染宿主的中枢神经系统（CNS）引发炎症反应，导致髓鞘形成异常、脱髓鞘和神经元丧失。反式激活蛋白Tat的碱性结构域与中枢神经系统损伤有关。向侧脑室（全身注射）或灰质（即海马体和丘脑，局部注射）注入含碱性结构域的Tat肽，会引发炎症过程，其特征为形成水肿、巨噬细胞浸润并伴有反应性星形胶质细胞增生。源自慢病毒蛋白或无关蛋白（如卵清蛋白）的对照肽不会引发任何炎症反应或细胞死亡。炎症导致侧脑室室管膜细胞和灰质神经元丧失。从注射Tat的半球提取的RNA与肿瘤坏死因子-α（TNF-α）、白细胞介素-1α和β（IL-1α和β）以及白细胞介素-6（IL-6）探针发生反应。巨噬细胞/小胶质细胞诱导型一氧化氮合酶也有表达。用己酮可可碱治疗阻断TNF-α会导致IL-1和诱导型一氧化氮合酶表达降低，同时病变体积减小，这表明Tat诱导的病变可能由TNF产生介导。
