Helicobacter pylori Reactivates Human Immunodeficiency Virus-1 in Latently Infected Monocytes with Increased Expression of IL-1β and CXCL8

Author(s): Vidhya Natarajan, Preeti Moar, Urvinder S. Kaur, Vimala Venkatesh, Abhishek Kumar, Rupesh Chaturvedi, D. Himanshu, Ravi Tandon*.

Journal Name: Current Genomics

Volume 20 , Issue 8 , 2019

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Graphical Abstract:


Abstract:

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.

Keywords: HIV, ART, LRA, Helicobacter pylori, gene expression, infected monocytes.

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VOLUME: 20
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