Opioid abuse alters the functions of immune cells in both in vitro and in vivo systems, including macrophages. Here, we investigated the effects of methadone, a widely used opioid receptor agonist for treatment of opiate addiction, on the expression of intracellular viral restriction factors and HIV replication in primary human macrophages. We showed that methadone enhanced the HIV infectivity in primary human macrophages. Mechanistically, methadone treatment of macrophages reduced the expression of interferons (IFN-β and IFN-λ2) and the IFN-stimulated anti-HIV genes (APOBEC3F/G and MxB). In addition, methadone-treated macrophages showed lower levels of several anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, and miR-155) compared to untreated cells. Exogenous IFN-β treatment restored the methadone-induced reduction in the expression of the above genes. These effects of methadone on HIV and the antiviral factors were antagonized by pretreatment of cells with naltrexone. These findings provide additional evidence to support further studies on the role of opiates, including methadone, in the immunopathogenesis of HIV disease.

阿片类药物滥用会改变两者的免疫细胞功能 体外 和 体内系统，包括巨噬细胞。在这里，我们调查了美沙酮（一种广泛用于治疗阿片成瘾的阿片受体激动剂）对人原代巨噬细胞中细胞内病毒限制因子表达和HIV复制的影响。我们表明，美沙酮可增强人类原代巨噬细胞的HIV感染力。从机理上讲，美沙酮治疗巨噬细胞可降低干扰素（IFN-β和IFN-λ2）和IFN刺激的抗HIV基因（APOBEC3F / G和MxB）的表达。此外，与未经处理的细胞相比，美沙酮处理的巨噬细胞显示出较低水平的几种抗HIV microRNA（miRNA-28，miR-125b，miR-150和miR-155）。外源IFN-β治疗恢复了美沙酮诱导的上述基因表达的降低。美沙酮对艾滋病毒和抗病毒因子的这些作用通过用纳曲酮预处理细胞而被拮抗。这些发现提供了更多的证据，以支持对包括美沙酮在内的鸦片剂在HIV疾病的免疫发病机制中的作用的进一步研究。