HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway

Planès, Rémi; Serrero, Manutea; Leghmari, Kaoutar; BenMohamed, Lbachir; Bahraoui, Elmostafa

doi:10.1038/s41598-018-35478-1

Cited by 36 publications

(28 citation statements)

References 87 publications

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“…It initiates transcription by recruiting Histone acetyltransferases to the HIV-LTR [76]. Consistent with increased transcription level, an induction of downstream proinflammatory cytokines, IL-1β, IL-6, and TNF-α was also observed during HIV-1 infection in several in vitro studies [77][78][79]. Our study also revealed that in addition to live/intact bacteria, heat-killed H. pylori can also reactivate HIV transcription.…”

Section: Discussionsupporting

confidence: 81%

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

Natarajan

Moar

Kaur

et al. 2020

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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. Method: 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.

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Section: Discussionsupporting

confidence: 81%

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

Natarajan

Moar

Kaur

et al. 2020

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“…Prolonged abnormal presence of IFN-γ reduced heme oxygenase-1 expression in human astrocytes, which contributes to oxidative stress, another pathogenic characteristic of HAND [79]. Several previous studies have found that HIV viral genes induce the expression of IL-10; however, in the Tg26 mouse model [80][81][82], we found the opposite. DHF upregulated IL-10, similar to our previous ndings in a murine model for multiple sclerosis, a neurodegenerative disease [23].…”

Section: Discussioncontrasting

confidence: 65%

7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

Bryant

Andhavarapu

Bever

et al. 2020

Preprint

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Background: The combined antiretroviral therapy (cART) era has significantly increased the lifespan of HIV patients, turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In HIV+ patients, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile.Methods: We investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. We immunohistochemically stained brain tissue sections from vehicle-treated wild type (WT), vehicle-treated Tg26, and DHF (5 mg/kg, i.p)-treated Tg26 mice to examine activation of TrkB and downstream signaling, expression of HIV-1 chemokine co-receptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. A one-way ANOVA with a Bonferroni Comparison post-hoc test was performed to analyze the data sets. Results: In the brain regions of Tg26 mice, we observed astrogliosis, increased CXCR4 and CCR5 expression, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks.Conclusions: Our study provides an overview of how targeting BDNF-TrkB signaling in the pathophysiology of HAND may be relevant for future therapies, and sheds light on 7,8 Dihydroxyflavone as a potential adjunct therapeutic agent to current antiviral therapy.

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“…HIV-1 gp120 and tat activate expression of proinflammatory cytokines, including tumor necrosis factor alpha [158, 159], which may stimulate EMT [97–100].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 proteins gp120 and tat induce the epithelial–mesenchymal transition in oral and genital mucosal epithelial cells

et al. 2019

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The oral, cervical, and genital mucosa, covered by stratified squamous epithelia with polarized organization and strong tight and adherens junctions, play a critical role in preventing transmission of viral pathogens, including human immunodeficiency virus (HIV). HIV-1 interaction with mucosal epithelial cells may depolarize epithelia and disrupt their tight and adherens junctions; however, the molecular mechanism of HIV-induced epithelial disruption has not been completely understood. We showed that prolonged interaction of cell-free HIV-1 virions, and viral envelope and transactivator proteins gp120 and tat, respectively, with tonsil, cervical, and foreskin epithelial cells induces an epithelial–mesenchymal transition (EMT). EMT is an epigenetic process leading to the disruption of mucosal epithelia and allowing the paracellular spread of viral and other pathogens. Interaction of cell-free virions and gp120 and tat proteins with epithelial cells substantially reduced E-cadherin expression and activated vimentin and N-cadherin expression, which are well-known mesenchymal markers. HIV gp120- and tat-induced EMT was mediated by SMAD2 phosphorylation and activation of transcription factors Slug, Snail, Twist1 and ZEB1. Activation of TGF-β and MAPK signaling by gp120, tat, and cell-free HIV virions revealed the critical roles of these signaling pathways in EMT induction. gp120- and tat-induced EMT cells were highly migratory via collagen-coated membranes, which is one of the main features of mesenchymal cells. Inhibitors of TGF-β1 and MAPK signaling reduced HIV-induced EMT, suggesting that inactivation of these signaling pathways may restore the normal barrier function of mucosal epithelia.

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HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway

Cited by 36 publications

References 87 publications

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

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

7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder

HIV-1 proteins gp120 and tat induce the epithelial–mesenchymal transition in oral and genital mucosal epithelial cells

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