Vitamin D boosts HIV-1 resistance in female genital epithelial cells by enhancing antiviral cathelicidin expression

Introduction: Elevated levels of serum Vitamin D (VitD) and increased expression of its receptor on peripheral blood cells have been reported in individuals who have been exposed to HIV-1 yet remain seronegative (HESN). This study aimed to investigate the potential antiviral role of VitD in the female genital epithelium, which constitutes the first physical barrier against HIV-1. We hypothesized that VitD may modulate susceptibility to HIV-1 infection by influencing epithelial functions such as tight junction integrity, production of antiviral peptides, and secretion of pro-inflammatory mediators. Methods: M). After VitD removal, HIV-1 were added to the apical chamber, and CD4+ T cells (HIV targets) were placed in the basal chamber. HIV-1 transmigration and infection of CD4+ T cells were quantified. CAMP (cathelicidin) transcript levels and protein secretion were also measured. Results: Pre-treatment of End1, Ect1 and Vk2 epithelial monolayers with VitD reduced HIV-infection of the CD4+ T cells in the basal chamber by 50%, 53%, and 31%, respectively. Only a fraction of the HIV-1 virion applied apically transmigrated across the epithelium. The infectivity of the residual apical HIV-1 virion in the VitD-pre-treated End1, Ect1, and VK2 cultures was reduced by 42%, 36%, and 25%, respectively. These reductions were accompanied by increased RNA transcripts encoding Cathelicidin Antimicrobial Peptide (CAMP) and elevated secretion of CAMP protein into the apical chamber. Conclusion: These findings provide evidence that VitD enhances the antiviral properties of female genital epithelium and reduces HIV-1 infectivity.