Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Medicine, Infectious Diseases Division, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
J Neurovirol. 2018 Aug;24(4):398-410. doi: 10.1007/s13365-018-0629-1. Epub 2018 Mar 28.
The widespread use of antiretroviral therapy for treatment of human immunodeficiency virus (HIV) infections has dramatically improved the quality and duration of life for HIV-positive individuals. Despite this success, HIV persists for the life of an infected person in tissue reservoirs including the nervous system. Thus, whether HIV exacerbates age-related brain disorders such as Parkinson's disease (PD) is of concern. In support of this idea, HIV infection can be associated with motor and gait abnormalities that parallel late-stage manifestations of PD including dopaminergic neuronal loss. With these findings in hand, we investigated whether viral infection could affect nigrostriatal degeneration or exacerbate chemically induced nigral degeneration. We now demonstrate an additive effect of EcoHIV on dopaminergic neuronal loss and neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. HIV-1-infected humanized mice failed to recapitulate these EcoHIV results suggesting species-specific neural signaling. The results demonstrate a previously undefined EcoHIV-associated neurodegenerative response that may be used to model pathobiological aspects of PD.
抗逆转录病毒疗法在治疗人类免疫缺陷病毒（HIV）感染方面的广泛应用，显著提高了 HIV 阳性个体的生活质量和寿命。尽管取得了这一成功，但 HIV 仍存在于包括神经系统在内的组织储库中，伴随感染者终生。因此，HIV 是否会加重帕金森病（PD）等与年龄相关的大脑疾病，这一点令人担忧。支持这一观点的是，HIV 感染可导致运动和步态异常，与 PD 的晚期表现（包括多巴胺能神经元丧失）相平行。鉴于这些发现，我们研究了病毒感染是否会影响黑质纹状体变性或加重化学诱导的黑质变性。我们现在证明，EcoHIV 对 1-甲基-4-苯基-1,2,3,6-四氢吡啶中毒引起的多巴胺能神经元丧失和神经炎症有叠加作用。感染 HIV-1 的人源化小鼠未能重现这些 EcoHIV 结果，这表明存在物种特异性的神经信号。这些结果表明存在一种以前未定义的与 EcoHIV 相关的神经退行性反应，可用于模拟 PD 的病理生物学方面。
