Vitamin D3 inhibits TNFα-induced latent HIV reactivation in J-LAT cells.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to suppress NF-kB activity by interfering with its pathways. The aim of this study was to investigate the ability of 1,25(OH)2D3 in reducing the reactivation of the HIV virus J-LAT cells, an established model of latently infected cells, which were treated with TNFalpha (100 ng/ml) for 2 h with or without 24 h 1,25(OH)2D3 (100 nM) pretreatment. Reactivation of HIV RNA in J-LAT was evaluated in terms of green fluorescent protein (GFP) expression. The same experimental setting was repeated on T cells from HIV-infected patients. Treatment with TNFalpha was associated with a 16 % increase in GFP+ cells and a five-fold increase in unspliced HIV RNA expression (p < 0.04). Pretreatment of J-LAT cells with 1,25(OH)2D3 for 24 h followed by TNFalpha (100 ng/ml) for 2 h reduced the percentage of GFP+ cells by 8 %; moreover, a 2.4-fold decrease in unspliced HIV RNA expression was observed (p < 0.002). In T cells from patients, treatment with TNFalpha significantly increased unspliced HIV RNA expression (sixfold increase, p < 0.02), whereas prestimulation with 1,25(OH)2D3 reduced its expression (2.5-fold decrease, p < 0.02) compared to controls.1,25(OH)2D3 is able to reduce the ability of TNFalpha to upregulate the transcription of HIV RNA from latently infected cells. These data provide further understanding of the pathogenic mechanisms regulating viral reactivation from latent reservoirs, along with new insight in viral internalization.
Unit of Infectious Diseases, Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy.
G
G
Nunnari
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
P
P
Fagone
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
F
F
Lazzara
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
A
A
Longo
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
D
D
Cambria
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
G
G
Di Stefano
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
M
M
Palumbo
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
L
L
Malaguarnera
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. mdirosa@unict.it.
Michelino
http://orcid.org/0000-0002-1837-9325
M
Di Rosa
D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014775:Virus Activation / Q000187:drug effects*
D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol
CD4+; HIV; J-LAT; Vitamin D3