Vitamin D Decreases Susceptibility of CD4+ 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 approaches. CD4+ T-cells from healthy male donors were treated with VitD and infected with HIV-1. After 72 hours, 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 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% (p=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 AKT1, CCNT1, SLC2A1, HIF1A and PFKL. In vitro, VitD reduced AKT phosphorylation by 26.6% (p=0.0156), transcription of CCNT1 by 22.7% (p=0.0391), and glucose uptake by 22.8% (p=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.