title: High Expression of Antiviral and Vitamin D Pathway Genes Are a Natural Characteristic of a Small Cohort of HIV-1-Exposed Seronegative Individuals.
abstract: Natural resistance to HIV-1 infection is influenced by genetics, viral-exposure, and endogenous immunomodulators such as vitamin D (VitD), being a multifactorial phenomenon that characterizes HIV-1-exposed seronegative individuals (HESNs). We compared mRNA expression of 10 antivirals, 5 immunoregulators, and 3 VitD pathway genes by qRT-PCR in cells of a small cohort of 11 HESNs, 16 healthy-controls (HCs), and 11 seropositives (SPs) at baseline, in response to calcidiol (VitD precursor) and/or aldithriol-2-(AT2)-inactivated HIV-1. In addition, the expression of TIM-3 on T and NK cells of six HCs after calcidiol and calcitriol (active VitD) treatments was evaluated by flow cytometry. Calcidiol increased the mRNA expression ofHAVCR2(TIM-3; Th1-cells inhibitor) in HCs and HESNs. AT2-HIV-1 increased the mRNA expression of the activating VitD enzymeCYP27B1, of the endogenous antiviral proteinsMX2, TRIM22, APOBEC3G, and of immunoregulatorsERAP2andHAVCR2, but reduced the mRNA expression of VitD receptor (VDR) and antiviral peptidesPI3andCAMPin all groups. Remarkably, higher mRNA levels ofVDR, CYP27B1, PI3, CAMP, SLPI, and ofERAP2were found in HESNs compared to HCs either at baseline or after stimuli. Furthermore, calcitriol increases the percentage of CD4+ T cells expressing TIM-3 protein compared to EtOH controls. These results suggest that high mRNA expression of antiviral and VitD pathway genes could be genetically determined in HESNs more than viral-induced at least in peripheral blood mononuclear cells. Moreover, the virus could potentiate bio-activation and use of VitD, maintaining the homeostasis of the immune system. Interestingly, VitD-induced TIM-3 on T cells, a T cell inhibitory and anti-HIV-1 molecule, requires further studies to analyze the functional outcomes during HIV-1 infection.
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; Dipartimento di Scienze Biomediche e Cliniche-Luigi Sacco, Università Degli Studi di Milano, Milan, Italy.
authors.forename: Wbeimar
authors.initials: W
authors.lastname: Aguilar-Jimenez
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche-Luigi Sacco, Università Degli Studi di Milano , Milan , Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Saulle
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche-Luigi Sacco, Università Degli Studi di Milano , Milan , Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.affiliation: Ospedale S. Maria Annunziata , Florence , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vichi
authors.affiliation: Ospedale S. Maria Annunziata , Florence , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.affiliation: Ospedale S. Maria Annunziata , Florence , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA , Medellín , Colombia.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rugeles
authors.affiliation: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy; Fondazione Don C. Gnocchi, IRCCS, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche-Luigi Sacco, Università Degli Studi di Milano , Milan , Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Biasin
keywords: HIV-1; HIV-1-exposed seronegative individuals; antiviral agents; natural resistance; vitamin D