title: Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro.
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 transcription-polymerase chain reaction.
  
  
  RESULTS
  Cholecalciferol decreased the frequency of HIV-1-infected p24CD4 T cells and levels of p24 in supernatants in a dose-dependent manner. Moreover, the CD4CD38HLA-DR and CD4CD38HLA-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 CD38HLA-DR but not of CD38HLA-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 cholecalciferol concentration, by promoting an HIV-1-restrictive CD38HLA-DR immunophenotype.
authors: *Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; †Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia; ‡Dipartimento di Scienze Biomediche e Cliniche- L. Sacco, Università Degli Studi di Milano, Milan, Italy; §Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy; and ‖Fondazione Don C. Gnocchi IRCCS, Milan, Italy.
authors: Wbeimar
authors: W
authors: Aguilar-Jimenez
authors: Simon
authors: S
authors: Villegas-Ospina
authors: Sandra
authors: S
authors: Gonzalez
authors: Wildeman
authors: W
authors: Zapata
authors: Irma
authors: I
authors: Saulle
authors: Micaela
authors: M
authors: Garziano
authors: Mara
authors: M
authors: Biasin
authors: Mario
authors: M
authors: Clerici
authors: Maria T
authors: MT
authors: Rugeles
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002112:Calcifediol / Q000494:pharmacology*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D003105:Colombia; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000821:virology; D008562:Membrane Glycoproteins / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D002762:Cholecalciferol; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002112:Calcifediol