Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach
Activated immune cells are highly susceptible to human immunodeficiency virus (HIV) infection. Vitamin D (VitD) induces antimicrobial responses and reduces cellular activation. We investigated VitD effects on HIV-1 replication, glucose uptake, and gene regulation using computational and in vitro app...
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MDPI AG
2025-03-01
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| author | John D. Loaiza Jose Fernando Gómez Daniel Muñoz-Escudero Sandra M. Gonzalez Timothy Kyle Eubank Maria T. Rugeles Ana Lucía Rodríguez-Perea Wbeimar Aguilar-Jimenez |
| author_facet | John D. Loaiza Jose Fernando Gómez Daniel Muñoz-Escudero Sandra M. Gonzalez Timothy Kyle Eubank Maria T. Rugeles Ana Lucía Rodríguez-Perea Wbeimar Aguilar-Jimenez |
| author_sort | John D. Loaiza |
| collection | DOAJ |
| description | Activated immune cells are highly susceptible to human immunodeficiency virus (HIV) infection. Vitamin D (VitD) induces antimicrobial responses and reduces cellular activation. We investigated VitD effects on HIV-1 replication, glucose uptake, and gene regulation using computational and in vitro approaches. CD4<sup>+</sup> T cells from healthy male donors were treated with VitD and infected with HIV-1. After 72 h, p24 protein was measured to assess viral replication. VitD effects on anti- and pro-HIV genes were analyzed by a Boolean network model based on curated databases and the literature. CCR5 and CXCR4 coreceptor expression, AKT phosphorylation, and glucose uptake were evaluated by flow cytometry, and expression of some model-identified genes was quantified by qPCR. VitD reduced p24 by 53.2% (<i>p</i> = 0.0078). Boolean network modeling predicted that VitD upregulates antiviral, migration, and cell-differentiation related genes, while downregulating genes related to cellular activation, proliferation, glucose metabolism, and HIV replication, notably <i>AKT1, CCNT1, SLC2A1, HIF1A,</i> and <i>PFKL</i>. In vitro, VitD reduced AKT phosphorylation by 26.6% (<i>p</i> = 0.0156), transcription of <i>CCNT1</i> by 22.7% (<i>p</i> = 0.0391), and glucose uptake by 22.8% (<i>p</i> = 0.0039) without affecting classic antiviral genes or coreceptor expression. These findings suggest an anti-HIV effect of VitD, mediated through AKT and glucose metabolism downmodulation, both involved in cell activation and HIV-1 replication. |
| format | Article |
| id | doaj-art-ae599db024894df7ad666d05568b04c9 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-ae599db024894df7ad666d05568b04c92025-08-20T02:11:18ZengMDPI AGBiomolecules2218-273X2025-03-0115343210.3390/biom15030432Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro ApproachJohn D. Loaiza0Jose Fernando Gómez1Daniel Muñoz-Escudero2Sandra M. Gonzalez3Timothy Kyle Eubank4Maria T. Rugeles5Ana Lucía Rodríguez-Perea6Wbeimar Aguilar-Jimenez7Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaSexually Transmitted and Blood-Borne Infections Division at JC Wilt Infectious Diseases Research Centre, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, CanadaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaGrupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín 050010, ANT, ColombiaActivated immune cells are highly susceptible to human immunodeficiency virus (HIV) infection. Vitamin D (VitD) induces antimicrobial responses and reduces cellular activation. We investigated VitD effects on HIV-1 replication, glucose uptake, and gene regulation using computational and in vitro approaches. CD4<sup>+</sup> T cells from healthy male donors were treated with VitD and infected with HIV-1. After 72 h, p24 protein was measured to assess viral replication. VitD effects on anti- and pro-HIV genes were analyzed by a Boolean network model based on curated databases and the literature. CCR5 and CXCR4 coreceptor expression, AKT phosphorylation, and glucose uptake were evaluated by flow cytometry, and expression of some model-identified genes was quantified by qPCR. VitD reduced p24 by 53.2% (<i>p</i> = 0.0078). Boolean network modeling predicted that VitD upregulates antiviral, migration, and cell-differentiation related genes, while downregulating genes related to cellular activation, proliferation, glucose metabolism, and HIV replication, notably <i>AKT1, CCNT1, SLC2A1, HIF1A,</i> and <i>PFKL</i>. In vitro, VitD reduced AKT phosphorylation by 26.6% (<i>p</i> = 0.0156), transcription of <i>CCNT1</i> by 22.7% (<i>p</i> = 0.0391), and glucose uptake by 22.8% (<i>p</i> = 0.0039) without affecting classic antiviral genes or coreceptor expression. These findings suggest an anti-HIV effect of VitD, mediated through AKT and glucose metabolism downmodulation, both involved in cell activation and HIV-1 replication.https://www.mdpi.com/2218-273X/15/3/432HIVvitamin Dglucose uptakeBoolean modelingprotein kinase BAKT signaling |
| spellingShingle | John D. Loaiza Jose Fernando Gómez Daniel Muñoz-Escudero Sandra M. Gonzalez Timothy Kyle Eubank Maria T. Rugeles Ana Lucía Rodríguez-Perea Wbeimar Aguilar-Jimenez Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach Biomolecules HIV vitamin D glucose uptake Boolean modeling protein kinase B AKT signaling |
| title | Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach |
| title_full | Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach |
| title_fullStr | Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach |
| title_full_unstemmed | Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach |
| title_short | Vitamin D Decreases Susceptibility of CD4<sup>+</sup> T Cells to HIV Infection by Reducing AKT Phosphorylation and Glucose Uptake: A Bioinformatic and In Vitro Approach |
| title_sort | vitamin d decreases susceptibility of cd4 sup sup t cells to hiv infection by reducing akt phosphorylation and glucose uptake a bioinformatic and in vitro approach |
| topic | HIV vitamin D glucose uptake Boolean modeling protein kinase B AKT signaling |
| url | https://www.mdpi.com/2218-273X/15/3/432 |
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