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生态 HIV 脑感染的大鼠模型。

A Rat Model of EcoHIV Brain Infection.

机构信息

Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina.

Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina;

出版信息

J Vis Exp. 2021 Jan 21(167). doi: 10.3791/62137.

Abstract

It has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV). First, the lentiviral construct of EcoHIV was packaged in cultured 293 FT cells for 48 hours. Then, the conditional medium was concentrated and titered. Next, we performed bilateral stereotaxic injections of the EcoHIV-EGFP into F344/N rat brain tissue. One week after infection, EGFP fluorescence signals were detected in the infected brain tissue, indicating that EcoHIV successfully induces an active HIV infection in rats. In addition, immunostaining for the microglial cell marker, Iba1, was performed. The results indicated that microglia were the predominant cell type harboring EcoHIV. Furthermore, EcoHIV rats exhibited alterations in temporal processing, a potential underlying neurobehavioral mechanism of HAND as well as synaptic dysfunction eight weeks after infection. Collectively, the present study extends the EcoHIV model of HIV-1 infection to the rat offering a valuable biological system to study HIV-1 viral reservoirs in the brain as well as HAND and associated comorbidities such as drug abuse.

摘要

已经有充分的研究表明,EcoHIV 感染小鼠模型在研究 HIV 相关神经并发症方面具有重要的应用价值。建立用于研究药物滥用和神经认知障碍的 EcoHIV 感染大鼠模型,将有助于研究神经 HIV 和 HIV-1 相关神经认知障碍(HAND)。在本研究中,我们成功地使用嵌合 HIV(EcoHIV)建立了活性 HIV 感染大鼠模型。首先,将 EcoHIV 的慢病毒构建体在培养的 293FT 细胞中包装 48 小时。然后,浓缩并滴定条件培养基。接下来,我们对 F344/N 大鼠脑组织进行双侧立体定向注射 EcoHIV-EGFP。感染后 1 周,在感染的脑组织中检测到 EGFP 荧光信号,表明 EcoHIV 成功诱导大鼠发生活性 HIV 感染。此外,还进行了小胶质细胞标志物 Iba1 的免疫染色。结果表明,小胶质细胞是携带 EcoHIV 的主要细胞类型。此外,感染 8 周后,EcoHIV 大鼠表现出时间处理的改变,这是 HAND 以及突触功能障碍的潜在神经行为机制之一。总之,本研究将 HIV-1 感染的 EcoHIV 模型扩展到大鼠,为研究大脑中的 HIV-1 病毒储库以及 HAND 及其相关合并症(如药物滥用)提供了有价值的生物学系统。

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