Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection
Traditional medicine is often chosen due to its affordability, its familiarity with patient’s cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-k...
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2021-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.620038/full |
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doaj-325baf33ad344173b830fc12fe10e23c2021-02-11T06:09:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-02-011110.3389/fphar.2020.620038620038Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV InfectionAntonella Minutolo0Marina Potestà1Valentina Roglia2Marco Cirilli3Marco Cirilli4Federico Iacovelli5Carlotta Cerva6Joseph Fokam7Alessandro Desideri8Massimo Andreoni9Sandro Grelli10Vittorio Colizzi11Vittorio Colizzi12Rosario Muleo13Carla Montesano14Department of Biology, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Agricultural and Forestry Science, University of Tuscia, Viterbo, ItalyDepartment of Agricultural and Environmental Sciences, University of Milan, Milan, ItalyDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyDepartment of System Medicine, University of Rome “Tor Vergata”, Rome, ItalyChantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, CameroonDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyDepartment of System Medicine, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Experimental Medicine, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyFaculty of Sciences and Technology, Evangelic University of Cameroon, Bandjoun, CameroonDepartment of Agricultural and Forestry Science, University of Tuscia, Viterbo, ItalyDepartment of Biology, University of Rome “Tor Vergata”, Rome, ItalyTraditional medicine is often chosen due to its affordability, its familiarity with patient’s cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-kingdom manner. The aim of the study was to evaluate the effects of plant-enriched purified extract microRNAs from Moringa oleifera seeds (MO) on the immune response and on HIV infection. Bioinformatic analysis shows that plant microRNAs (p-miRs) from MO belonging to 18 conserved families, including p-miR160h, p-miR166, p-miR482b, p-miR159c, p-miR395d, p-miR2118a, p-miR393a, p-miR167f-3p, and p-miR858b are predicted to target with high affinity BCL2, IL2RA, TNF, and VAV1, all these being involved in the cell cycle, apoptosis, immune response and also in the regulation of HIV pathogenesis. The effects of MO p-miRs transfected into HIV+ PBMCs were analyzed and revealed a decrease in viability associated with an increase of apoptosis; an increase of T helper cells expressing Fas and a decrease of intracellular Bcl2 protein expression. Meanwhile no effects were detected in PBMCs from healthy donors. In CD4+ T cells, transfection significantly reduced cell activation and modified the T cell differentiation, thereby decreasing both central and effector memory cells while increasing terminal effector memory cells. Interestingly, the p-miRs transfection induces a reduction of intracellular HIV p24 protein and a reduction of viral DNA integration. Finally, we evaluated the effect of synthetic (mimic) p-miR858b whose sequence is present in the MO p-miR pool and predicted to target VAV1, a protein involved in HIV-Nef binding. This protein plays a pivotal role in T cell antigen receptor (TCR) signaling, so triggering the activation of various pathways. The transfection of HIV+ PBMCs with the synthetic p-miR858b showed a reduced expression of VAV1 and HIV p24 proteins. Overall, our evidence defines putative mechanisms underlying a supplementary benefit of traditional medicine, alongside current antiretroviral therapy, in managing HIV infection in resource-limited settings where MO remains widely available.https://www.frontiersin.org/articles/10.3389/fphar.2020.620038/fullHIVpost-transcription regulationMoringa oleferiacross-kingdomimmune response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonella Minutolo Marina Potestà Valentina Roglia Marco Cirilli Marco Cirilli Federico Iacovelli Carlotta Cerva Joseph Fokam Alessandro Desideri Massimo Andreoni Sandro Grelli Vittorio Colizzi Vittorio Colizzi Rosario Muleo Carla Montesano |
spellingShingle |
Antonella Minutolo Marina Potestà Valentina Roglia Marco Cirilli Marco Cirilli Federico Iacovelli Carlotta Cerva Joseph Fokam Alessandro Desideri Massimo Andreoni Sandro Grelli Vittorio Colizzi Vittorio Colizzi Rosario Muleo Carla Montesano Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection Frontiers in Pharmacology HIV post-transcription regulation Moringa oleferia cross-kingdom immune response |
author_facet |
Antonella Minutolo Marina Potestà Valentina Roglia Marco Cirilli Marco Cirilli Federico Iacovelli Carlotta Cerva Joseph Fokam Alessandro Desideri Massimo Andreoni Sandro Grelli Vittorio Colizzi Vittorio Colizzi Rosario Muleo Carla Montesano |
author_sort |
Antonella Minutolo |
title |
Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection |
title_short |
Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection |
title_full |
Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection |
title_fullStr |
Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection |
title_full_unstemmed |
Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection |
title_sort |
plant micrornas from moringa oleifera regulate immune response and hiv infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-02-01 |
description |
Traditional medicine is often chosen due to its affordability, its familiarity with patient’s cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-kingdom manner. The aim of the study was to evaluate the effects of plant-enriched purified extract microRNAs from Moringa oleifera seeds (MO) on the immune response and on HIV infection. Bioinformatic analysis shows that plant microRNAs (p-miRs) from MO belonging to 18 conserved families, including p-miR160h, p-miR166, p-miR482b, p-miR159c, p-miR395d, p-miR2118a, p-miR393a, p-miR167f-3p, and p-miR858b are predicted to target with high affinity BCL2, IL2RA, TNF, and VAV1, all these being involved in the cell cycle, apoptosis, immune response and also in the regulation of HIV pathogenesis. The effects of MO p-miRs transfected into HIV+ PBMCs were analyzed and revealed a decrease in viability associated with an increase of apoptosis; an increase of T helper cells expressing Fas and a decrease of intracellular Bcl2 protein expression. Meanwhile no effects were detected in PBMCs from healthy donors. In CD4+ T cells, transfection significantly reduced cell activation and modified the T cell differentiation, thereby decreasing both central and effector memory cells while increasing terminal effector memory cells. Interestingly, the p-miRs transfection induces a reduction of intracellular HIV p24 protein and a reduction of viral DNA integration. Finally, we evaluated the effect of synthetic (mimic) p-miR858b whose sequence is present in the MO p-miR pool and predicted to target VAV1, a protein involved in HIV-Nef binding. This protein plays a pivotal role in T cell antigen receptor (TCR) signaling, so triggering the activation of various pathways. The transfection of HIV+ PBMCs with the synthetic p-miR858b showed a reduced expression of VAV1 and HIV p24 proteins. Overall, our evidence defines putative mechanisms underlying a supplementary benefit of traditional medicine, alongside current antiretroviral therapy, in managing HIV infection in resource-limited settings where MO remains widely available. |
topic |
HIV post-transcription regulation Moringa oleferia cross-kingdom immune response |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2020.620038/full |
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