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

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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomolecules
Subjects:
HIV
vitamin D
glucose uptake
Boolean modeling
protein kinase B
AKT signaling
Online Access:https://www.mdpi.com/2218-273X/15/3/432
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Summary: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.
ISSN:2218-273X

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