Natarajan Vidhya, Moar Preeti, Kaur Urvinder S, Venkatesh Vimala, Kumar Abhishek, Chaturvedi Rupesh, Himanshu D, Tandon Ravi
1Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India; 2Department of Microbiology, King Georges Medical University, Lucknow, India; 3Institute of Bioinformatics, International Technology Park, Bangaluru, 560066, India; 4Manipal Academy of Higher Education (MAHE), Manipal576104, Karnataka, India; 5Host Pathogen Interaction Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India; 6Department of Medicine, King Georges Medical University, Lucknow, India.
Curr Genomics. 2019 Dec;20(8):556-568. doi: 10.2174/1389202921666191226091138.
are gram-negative bacteria, which colonize the human stomach. More than 50% of the world's population is infected by . Based on the high prevalence of , it is very likely that HIV and infection may coexist. However, the molecular events that occur during HIV- co-infection remain unclear. Latent HIV reservoirs are the major obstacle in HIV cure despite effective therapy. Here, we explored the effect of stimulation on latently HIV-infected monocytic cell line U1.
High throughput RNA-Seq using Illumina platform was performed to analyse the change in transcriptome between unstimulated and -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.
stimulation increased the expression of HIV-1 Gag, both at transcription (p<0.001) and protein level. stimulation also increased the expression of proinflammatory cytokines IL-1β, CXCL8 and CXCL10 (p<0.0001). Heat-killed retained their ability to induce HIV transcription. RNA-Seq analysis revealed 197 significantly upregulated and 101 significantly downregulated genes in -stimulated U1 cells. IL-1β and CXCL8 were found to be significantly upregulated using transcriptome analysis, which was consistent with real-time PCR data.
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 studies elucidating the effect of in HIV latency and pathogenesis.
是革兰氏阴性菌，可定植于人的胃部。世界上超过50%的人口感染了。鉴于的高流行率，HIV与感染很可能同时存在。然而，HIV合并感染期间发生的分子事件仍不清楚。尽管有有效的治疗方法，但潜伏的HIV储存库仍是治愈HIV的主要障碍。在此，我们探讨了刺激对潜伏感染HIV的单核细胞系U1的影响。
使用Illumina平台进行高通量RNA测序，以分析未刺激和刺激的潜伏感染HIV的U1细胞之间转录组的变化。转录组分析使用生物信息学工具鉴定参与HIV潜伏逆转的潜在基因和途径，并通过实时PCR进行验证。
刺激在转录水平（p<0.001）和蛋白水平均增加了HIV-1 Gag的表达。刺激还增加了促炎细胞因子IL-1β、CXCL8和CXCL10的表达（p<0.0001）。热灭活的仍保留其诱导HIV转录的能力。RNA测序分析显示，刺激的U1细胞中有197个基因显著上调，101个基因显著下调。通过转录组分析发现IL-1β和CXCL8显著上调，这与实时PCR数据一致。
通过上调IL-1β和CXCL8重新激活潜伏感染单核细胞中的HIV-1，IL-1β和CXCL8是大多数炎症途径中重要的细胞因子。我们的结果为未来阐明在HIV潜伏和发病机制中的作用的研究提供了依据。
