Unmethylated CpG motifs activate toll-like receptor 9 (TLR9), leading to sequence- and species-specific immune stimulation. Here, we engineered a CpG oligodeoxyribonucleotide (ODN) with multiple hydrophobic moieties, so-called lipid-modified uracil, which resulted in a facile micelle formation of the stimulant. The self-assembled CpG nanostructure (U4CpG) containing the ODN 2216 sequence was characterized by various spectroscopic and microscopic methods together with molecular dynamics simulations. Next, we evaluated the nano-immunostimulant for enhancement of anti-HIV immunity. U4CpG treatment induced activation of plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells in healthy human peripheral blood, which produced type I interferons (IFNs) and IFN-γ in human peripheral blood mononuclear cells (PBMCs). Moreover, we validated the activation and promotion efficacy of U4CpG in patient-derived blood cells, and HIV-1 spread was significantly suppressed by a low dosage of the immunostimulant. Furthermore, U4CpG-treated PBMC cultured medium elicited transcription of latent HIV-1 in U1 cells indicating that U4CpG reversed HIV-1 latency. Thus, the functions of U4CpG in eradicating HIV-1 by enhancing immunity and reversing latency make the material a potential candidate for clinical studies dealing with viral infection.

未甲基化的 CpG 基序激活 Toll 样受体 9 (TLR9​​)，导致序列和物种特异性免疫刺激。在这里，我们设计了一种具有多个疏水部分的 CpG 寡脱氧核糖核苷酸 (ODN)，即所谓的脂质修饰尿嘧啶，这导致兴奋剂容易形成胶束。包含 ODN 2216 序列的自组装 CpG 纳米结构 (U4CpG) 通过各种光谱和微观方法以及分子动力学模拟进行表征。接下来，我们评估了纳米免疫刺激剂对增强抗 HIV 免疫力的作用。U4CpG 治疗诱导健康人外周血中浆细胞样树突细胞 (pDC) 和自然杀伤 (NK) 细胞的活化，从而产生 I 型干扰素(IFNs) 和人外周血单核细胞 (PBMCs) 中的 IFN-γ。此外，我们验证了 U4CpG 在患者来源的血细胞中的激活和促进​​作用，低剂量的免疫刺激剂显着抑制了 HIV-1 的传播。此外，U4CpG 处理的 PBMC 培养基引发 U1 细胞中潜伏 HIV-1 的转录，表明 U4CpG 逆转了 HIV-1 潜伏期。因此，U4CpG 通过增强免疫力和逆转潜伏期来根除 HIV-1 的功能使该材料成为处理病毒感染的临床研究的潜在候选材料。