Background Helicobacter pylori are gram-negative bacteria, which colonize the human stomach. More than 50% of the world’s population is infected by H. pylori. Based on the high prevalence of H. pylori, it is very likely that HIV and H. pylori infection may coexist. However, the molecular events that occur during HIV-H. pylori co-infection remain unclear. Latent HIV reservoirs are the major obstacle in HIV cure despite effective therapy. Here, we explored the effect of H. pylori stimulation on latently HIV-infected monocytic cell line U1. Methods High throughput RNA-Seq using Illumina platform was performed to analyse the change in transcriptome between unstimulated and H. pylori-stimulated latently HIV-infected U1 cells. Transcriptome analysis identified potential genes and pathways involved in the reversal of HIV latency using bioinformatic tools that were validated by real-time PCR. Results H. pylori stimulation increased the expression of HIV-1 Gag, both at transcription (p<0.001) and protein level. H. pylori stimulation also increased the expression of proinflammatory cytokines IL-1β, CXCL8 and CXCL10 (p<0.0001). Heat-killed H. pylori retained their ability to induce HIV transcription. RNA-Seq analysis revealed 197 significantly upregulated and 101 significantly downregulated genes in H. pylori-stimulated U1 cells. IL-1β and CXCL8 were found to be significantly upregulated using transcriptome analysis, which was consistent with real-time PCR data. Conclusion H. pylori reactivate HIV-1 in latently infected monocytes with the upregulation of IL-1β and CXCL8, which are prominent cytokines involved in the majority of inflammatory pathways. Our results warrant future in vivo studies elucidating the effect of H. pylori in HIV latency and pathogenesis.

中文翻译：

---

幽门螺杆菌在潜伏感染的单核细胞中重新激活人类免疫缺陷病毒-1，增加 IL-1β 和 CXCL8 的表达

背景 幽门螺杆菌是革兰氏阴性菌，在人的胃中定殖。世界上超过 50% 的人口感染了幽门螺杆菌。基于 H. pylori 的高流行率，HIV 和 H. pylori 感染很可能同时存在。然而，在 HIV-H 期间发生的分子事件。pylori 合并感染尚不清楚。尽管有有效的治疗方法，潜伏的 HIV 宿主仍是 HIV 治愈的主要障碍。在这里，我们探讨了 H. pylori 刺激对潜伏 HIV 感染的单核细胞系 U1 的影响。方法 使用 Illumina 平台进行高通量 RNA-Seq，以分析未刺激和 H. pylori 刺激的潜伏 HIV 感染 U1 细胞之间转录组的变化。转录组分析使用通过实时 PCR 验证的生物信息学工具确定了参与逆转 HIV 潜伏期的潜在基因和途径。结果 H. pylori 刺激增加了 HIV-1 Gag 的表达，无论是在转录水平 (p<0.001) 还是在蛋白质水平。H. pylori 刺激还增加了促炎细胞因子 IL-1β、CXCL8 和 CXCL10 的表达（p<0.0001）。热杀死的幽门螺杆菌保留了它们诱导 HIV 转录的能力。RNA-Seq 分析显示幽门螺杆菌刺激的 U1 细胞中有 197 个显着上调和 101 个显着下调基因。使用转录组分析发现 IL-1β 和 CXCL8 显着上调，这与实时 PCR 数据一致。结论 H。幽门螺杆菌通过上调 IL-1β 和 CXCL8 重新激活潜伏感染的单核细胞中的 HIV-1，它们是参与大多数炎症通路的主要细胞因子。我们的结果保证了未来的体内研究，以阐明幽门螺杆菌在 HIV 潜伏期和发病机制中的作用。