Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, China.
Guangxi Collaborative Innovation Center for Biomedicine, Life Science Institute, Guangxi Medical University, Nanning, China.
Sci Rep. 2017 Oct 12;7(1):13071. doi: 10.1038/s41598-017-12066-3.
The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study. A total of 200 subjects were enrolled and divided into four groups as follows: Opiate+ HIV+ (50), Opiate- HIV+ (50), Opiate+ HIV- (50), and healthy control (Opiate- HIV-, 50). All HIV-infected subjects did not receive antiretroviral therapy while they were enrolled in the study. The results showed that opiate use was associated with higher viral load and lower CD4+ T cell count. Opiate use alone led to lower expression of TLR9, IRF7, and IFN-α at the protein level in PBMCs. Combined with HIV-1 infection, opiate use resulted in lower expression of MyD88, ISG56, and MxA. In addition, morphine treatment promoted HIV-1 replication in macrophages via inhibition of TLR9 pathway. Our data reveal that opiate use plays a cofactor role in pathogenesis of HIV-1 infection through inhibition of TLR9 pathway.
阿片类药物使用促进 HIV-1 感染的分子机制尚未完全阐明。TLR9 在许多免疫细胞中表达，包括单核细胞、巨噬细胞，这些细胞可以识别病毒和病毒产物，从而诱导抗病毒因子的产生并启动免疫反应。先前的研究表明，慢性病毒感染可以克服并损害 TLR9 途径。我们旨在通过一项基于人群的研究，探讨阿片类药物使用是否通过抑制 TLR9 途径增强 HIV 感染。共纳入 200 名受试者，并分为四组：阿片类药物+HIV+（50 人）、阿片类药物-HIV+（50 人）、阿片类药物+HIV-（50 人）和健康对照组（阿片类药物-HIV-，50 人）。所有 HIV 感染的受试者在入组研究时均未接受抗逆转录病毒治疗。结果显示，阿片类药物使用与更高的病毒载量和更低的 CD4+T 细胞计数相关。阿片类药物单独使用会导致 PBMC 中 TLR9、IRF7 和 IFN-α的蛋白表达降低。与 HIV-1 感染结合后，阿片类药物使用导致 MyD88、ISG56 和 MxA 的表达降低。此外，吗啡处理通过抑制 TLR9 途径促进巨噬细胞中的 HIV-1 复制。我们的数据表明，阿片类药物使用通过抑制 TLR9 途径在 HIV-1 感染的发病机制中起辅助因子作用。
