Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.

中文翻译：

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甲基苯丙胺增加 SIV 感染的小胶质细胞/巨噬细胞的比例，改变代谢途径，并提升细胞死亡途径：单细胞分析

物质使用障碍和 HIV 感染继续影响着许多人。两者都对大脑有不良影响，并且这两种情况经常并存。在大脑中，巨噬细胞和小胶质细胞可被 HIV 感染，这些细胞也是滥用药物（如精神兴奋剂甲基苯丙胺）作用的靶点。为了确定 HIV 和甲基苯丙胺的相互作用，我们从使用或不使用甲基苯丙胺治疗的感染 SIV 的恒河猴中分离出小胶质细胞和脑巨噬细胞。对细胞进行单细胞 RNA 测序，并通过统计和生物信息学分析对结果进行分析。在用甲基苯丙胺治疗的动物中，SIV 感染的小胶质细胞和/或巨噬细胞比例显着增加。此外，细胞死亡途径中的基因编码功能增加，脑源性神经营养因子通路受到抑制。受感染细胞中的基因表达模式并未与未感染细胞分开聚集，但由来自甲基苯丙胺处理动物的小胶质细胞和/或巨噬细胞组成的簇在神经炎症和代谢途径方面不同于由来自未治疗动物的细胞组成的簇。甲基苯丙胺会增加 SIV 对 CNS 的感染，并对感染和未感染的小胶质细胞和大脑巨噬细胞产生不利影响，突出表明 HIV 感染和药物滥用对大脑的双重和相互作用的危害。但是，由来自甲基苯丙胺处理过的动物的小胶质细胞和/或巨噬细胞组成的簇在神经炎症和代谢途径方面不同于由来自未处理动物的细胞组成的簇。甲基苯丙胺会增加 SIV 对 CNS 的感染，并对感染和未感染的小胶质细胞和大脑巨噬细胞产生不利影响，突出表明 HIV 感染和药物滥用对大脑的双重和相互作用的危害。但是，由来自甲基苯丙胺处理过的动物的小胶质细胞和/或巨噬细胞组成的簇在神经炎症和代谢途径方面不同于由来自未处理动物的细胞组成的簇。甲基苯丙胺会增加 SIV 对 CNS 的感染，并对感染和未感染的小胶质细胞和大脑巨噬细胞产生不利影响，突出表明 HIV 感染和药物滥用对大脑的双重和相互作用的危害。