Power C, Moench T, Peeling J, Kong P A, Langelier T
Department of Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Neuroscience. 1997 Apr;77(4):1175-85. doi: 10.1016/s0306-4522(96)00531-3.
Feline immunodeficiency virus, like human immunodeficiency virus type 1, is a retrolentivirus causing neurological disease and immune suppression. Primary neurological complications, including human immunodeficiency virus encephalopathy and peripheral neuropathy, and neuropathological changes, including gliosis, neuronal injury and multinucleated giant cells, have been described for human immunodeficiency virus type 1 infection. Excitatory amino acids have been implicated as a basis for human immunodeficiency virus encephalopathy and the accompanying neuronal injury. Here, we test our hypothesis that feline immunodeficiency virus infection results in glial activation accompanied by enhanced glutamatergic activity, causing neuronal loss. Neurological signs observed in naturally and experimentally infected animals included ataxia, aggressivity and reduced motor activity. Neuropathological changes included gliosis, perivascular cuffing and neuronal dropout in the brains of both experimentally and naturally infected animals, but not in uninfected animals. Feline immunodeficiency virus antigen and genome were detected in the brains of all experimentally and naturally infected animals. Proton nuclear magnetic resonance spectroscopy revealed significantly increased glutamate levels in the feline immunodeficiency virus-infected animals. In contrast, glutamate decarboxylase levels in GABAergic neurons were reduced in feline immunodeficiency virus-infected animals. These findings provide direct in vivo evidence for enhanced glutamate levels in conjunction with neuronal loss, supporting the hypothesis of glutamate-mediated neurotoxicity as a major mechanism in the neuropathogenesis of retrolentiviral infections.
猫免疫缺陷病毒与人类免疫缺陷病毒1型一样，是一种导致神经疾病和免疫抑制的逆转录病毒。人类免疫缺陷病毒1型感染可引发原发性神经并发症，包括人类免疫缺陷病毒脑病和周围神经病变，以及神经病理变化，包括胶质增生、神经元损伤和多核巨细胞。兴奋性氨基酸被认为是人类免疫缺陷病毒脑病及伴随的神经元损伤的基础。在此，我们检验我们的假设，即猫免疫缺陷病毒感染导致胶质细胞活化并伴有谷氨酸能活性增强，从而引起神经元丢失。在自然感染和实验感染的动物中观察到的神经症状包括共济失调、攻击性和运动活动减少。神经病理变化包括实验感染和自然感染动物大脑中的胶质增生、血管周围套叠和神经元脱失，但未感染动物中未出现这些变化。在所有实验感染和自然感染动物的大脑中均检测到猫免疫缺陷病毒抗原和基因组。质子核磁共振波谱显示，猫免疫缺陷病毒感染动物的谷氨酸水平显著升高。相比之下，猫免疫缺陷病毒感染动物中γ-氨基丁酸能神经元中的谷氨酸脱羧酶水平降低。这些发现为谷氨酸水平升高与神经元丢失同时存在提供了直接的体内证据，支持了谷氨酸介导的神经毒性是逆转录病毒感染神经发病机制中的主要机制这一假设。
