Mangus Lisa M, Dorsey Jamie L, Laast Victoria A, Hauer Peter, Queen Suzanne E, Adams Robert J, McArthur Justin C, Mankowski Joseph L
From the Departments of Molecular and Comparative Pathobiology (LMM, JLD, VAL, SEQ, RJA, JLM) and Neurology (PH, JCM, JLM), Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Neuropathol Exp Neurol. 2015 Jan;74(1):38-47. doi: 10.1097/NEN.0000000000000148.
Studies of neurologic diseases induced by simian immunodeficiency virus (SIV) in Asian macaques have contributed greatly to the current understanding of human immunodeficiency virus pathogenesis in the brain and peripheral nervous system. Detailed investigations into SIV-induced alterations in the spinal cord, a critical sensorimotor relay point between the brain and the peripheral nervous system, have yet to be reported. In this study, lumbar spinal cords from SIV-infected pigtailed macaques were examined to quantify SIV replication and associated neuroinflammation. In untreated SIV-infected animals, there was a strong correlation between amount of SIV RNA in the spinal cord and expression of the macrophage marker CD68 and the key proinflammatory mediators tumor necrosis factor and CCL2. We also found a significant correlation between SIV-induced alterations in the spinal cord and the degree of distal epidermal nerve fiber loss among untreated animals. Spinal cord changes (including elevated glial fibrillary acidic protein immunostaining and enhanced CCL2 gene expression) also were present in SIV-infected antiretroviral drug-treated animals despite SIV suppression. A fuller understanding of the complex virus and host factor dynamics in the spinal cord during human immunodeficiency virus infection will be critical in the development of new treatments for human immunodeficiency virus-associated sensory neuropathies and studies aimed at eradicating the virus from the central nervous system.
对亚洲猕猴中由猴免疫缺陷病毒（SIV）引发的神经疾病的研究，极大地促进了目前对人类免疫缺陷病毒在大脑和外周神经系统中发病机制的理解。然而，对于SIV感染导致脊髓（大脑与外周神经系统之间关键的感觉运动中继点）发生改变的详细研究尚未见报道。在本研究中，对感染SIV的猪尾猕猴的腰脊髓进行了检查，以量化SIV复制及相关的神经炎症。在未经治疗的感染SIV的动物中，脊髓中SIV RNA的量与巨噬细胞标志物CD68以及关键促炎介质肿瘤坏死因子和CCL2的表达之间存在很强的相关性。我们还发现，在未经治疗的动物中，SIV引起的脊髓改变与远端表皮神经纤维丧失程度之间存在显著相关性。尽管SIV受到抑制，但在接受抗逆转录病毒药物治疗的感染SIV的动物中也存在脊髓变化（包括胶质纤维酸性蛋白免疫染色增强和CCL2基因表达增强）。更全面地了解人类免疫缺陷病毒感染期间脊髓中复杂的病毒和宿主因子动态，对于开发针对人类免疫缺陷病毒相关感觉神经病变的新疗法以及旨在从中枢神经系统根除该病毒的研究至关重要。
