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|Title:||Precursor forms of vitamin D reduce HIV-1 infection in vitro|
|Author:||Aguilar Jiménez, Wbeimar|
Villegas Ospina, Simón
Rugeles, María T.
|Abstract:||Background: Although the anti-HIV-1 effects of vitamin D (VitD) have been reported, mechanisms behind such protection remain largely unexplored. Methods: The effects of two precursor forms (cholecalciferol/calciol at 0.01, 1 and 100 nM and calcidiol at 100 and 250 nM) on HIV-1 infection, immune activation, and gene expression were analyzed in vitro in cells of Colombian and Italian healthy donors. We quantified levels of released p24 by enzyme-linked immunosorbent assay, of intracellular p24 and cell-surface expression of CD38 and HLA-DR by flow cytometry, and mRNA expression of antiviral and immunoregulatory genes by real-time reverse transcriptionpolymerase chain reaction. Results: Cholecalciferol decreased the frequency of HIV-1-infected p24+CD4+ T cells and levels of p24 in supernatants in a dosedependent manner. Moreover, the CD4+CD38+HLA-DR+ and CD4+CD382HLA-DR+ subpopulations were more susceptible to infection but displayed the greatest cholecalciferol-induced decreases in infection rate by an X4-tropic strain. Likewise, cholecalciferol at its highest concentration decreased the frequency of CD382HLA-DR+ but not of CD38+HLA-DR+ T-cell subsets. Analyzing the effects of calcidiol, the main VitD source for immune cells and an R5-tropic strain as the most frequently transmitted virus, a reduction in HIV-1 productive infection was also observed. In addition, an increase in mRNA expression of APOBEC3G and PI3 and a reduction of TRIM22 and CCR5 expression, this latter positively correlated with p24 levels, was noted. Conclusions: VitD reduces HIV-1 infection in T cells possibly by inducing antiviral gene expression, reducing the viral co-receptor CCR5 and, at least at the highest holecalciferol concentration, by promoting an HIV-1-restrictive CD38+HLA-DR2 immunophenotype.|
|CC Licence:||Licencia CC|
|Citation:||Aguilar Jimenez, W., Villegas Ospina, S., Gonzalez, S., Zapata, W., Saulle, I., Garziano, M., … Rugeles, M. T. (2016). Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro. JAIDS Journal of Acquired Immune Deficiency Syndromes, 73(5). Retrieved from http://journals.lww.com/jaids/Fulltext/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspx|
|Appears in Collections:||Medicina|
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