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 of HAVCR2 (TIM-3; Th1-cells inhibitor) in HCs and HESNs. AT2-HIV-1 increased the mRNA expression of the activating VitD enzyme CYP27B1, of the endogenous antiviral proteins MX2, TRIM22, APOBEC3G, and of immunoregulators ERAP2 and HAVCR2, but reduced the mRNA expression of VitD receptor (VDR) and antiviral peptides PI3 and CAMP in all groups. Remarkably, higher mRNA levels of VDR, CYP27B1, PI3, CAMP, SLPI, and of ERAP2 were 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.
| Original language | English |
|---|---|
| Article number | 136 |
| Journal | Frontiers in Immunology |
| Volume | 8 |
| Issue number | FEB |
| DOIs | |
| Publication status | Published - Feb 13 2017 |
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Keywords
- Antiviral agents
- HIV-1
- HIV-1-exposed seronegative individuals
- Natural resistance
- Vitamin D
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
High expression of antiviral and vitamin D pathway genes are a natural characteristic of a small cohort of HIV-1-exposed seronegative individuals. / Aguilar-Jimenez, Wbeimar; Saulle, Irma; Trabattoni, Daria; Vichi, Francesca; Caputo, Sergio Lo; Mazzotta, Francesco; Rugeles, Maria Teresa; Clerici, Mario; Biasin, Mara.
In: Frontiers in Immunology, Vol. 8, No. FEB, 136, 13.02.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High expression of antiviral and vitamin D pathway genes are a natural characteristic of a small cohort of HIV-1-exposed seronegative individuals
AU - Aguilar-Jimenez, Wbeimar
AU - Saulle, Irma
AU - Trabattoni, Daria
AU - Vichi, Francesca
AU - Caputo, Sergio Lo
AU - Mazzotta, Francesco
AU - Rugeles, Maria Teresa
AU - Clerici, Mario
AU - Biasin, Mara
PY - 2017/2/13
Y1 - 2017/2/13
N2 - 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 of HAVCR2 (TIM-3; Th1-cells inhibitor) in HCs and HESNs. AT2-HIV-1 increased the mRNA expression of the activating VitD enzyme CYP27B1, of the endogenous antiviral proteins MX2, TRIM22, APOBEC3G, and of immunoregulators ERAP2 and HAVCR2, but reduced the mRNA expression of VitD receptor (VDR) and antiviral peptides PI3 and CAMP in all groups. Remarkably, higher mRNA levels of VDR, CYP27B1, PI3, CAMP, SLPI, and of ERAP2 were 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.
AB - 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 of HAVCR2 (TIM-3; Th1-cells inhibitor) in HCs and HESNs. AT2-HIV-1 increased the mRNA expression of the activating VitD enzyme CYP27B1, of the endogenous antiviral proteins MX2, TRIM22, APOBEC3G, and of immunoregulators ERAP2 and HAVCR2, but reduced the mRNA expression of VitD receptor (VDR) and antiviral peptides PI3 and CAMP in all groups. Remarkably, higher mRNA levels of VDR, CYP27B1, PI3, CAMP, SLPI, and of ERAP2 were 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.
KW - Antiviral agents
KW - HIV-1
KW - HIV-1-exposed seronegative individuals
KW - Natural resistance
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=85014360154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014360154&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.00136
DO - 10.3389/fimmu.2017.00136
M3 - Article
AN - SCOPUS:85014360154
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - FEB
M1 - 136
ER -