Vitamin D regulates the expression of immune and stress response genes in dengue virus-infected macrophages by inducing specific microRNAs

MicroRNA ◽  
2021 ◽  
Vol 11 ◽  
Author(s):  
Geysson Javier Fernandez ◽  
Jorge Andrés Castillo ◽  
Diana Marcela Giraldo ◽  
Silvio Urcuqui-Inchima
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Stress Response ◽  
Dengue Virus ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Denv Infection ◽  
High Dose ◽  
Regulatory Pathways ◽  
Stress Response Genes

Background: The pathogenesis associated with Dengue virus (DENV) infection is marked by the impairment of host immune response. Consequently, the modulation of immune response has emerged as an important therapeutic target for the control of DENV infection. Vitamin D has been shown to regulate the immune response in DENV infection, although the molecular mechanism remains poorly understood. Post-transcriptional regulation of mRNA by miRNAs offers an opportunity to gain insight into the immunomodulation mediated by vitamin D Objective: Previously, it has been observed that a high dose of vitamin D (4000 IU) decreased DENV-2 infection and inflammatory response in monocyte-derived macrophages (MDMs). Here, we examine whether high or low doses of vitamin D supplements exert differential effect on miRNA expression in DENV-infected macrophages Methods: We analyzed miRNA expression profiles in MDMs isolated from healthy individuals who were given either 1000 or 4000 IU/day of vitamin D for 10 days. MDMs before or after vitamin D supplementation were challenged with DENV-2, and miRNAs profiles were analyzed by qPCR arrays. Results: DENV-2 infected MDMs supplemented with 4000 IU, showed up-regulation of miR-374a-5p, miR-363-3p, miR-101-3p, miR-9-5p, miR-34a-5p, miR-200a-3p, and the family of miRNAs miR-21-5p, and miR-590-p. The miRNA profile and predicted target mRNAs suggested regulatory pathways in MDMs obtained from healthy donors who received higher doses of vitamin D. These DENV-2 infected MDMs expressed a unique set of miRNAs that target immune and cellular stress response genes. Conclusion: The results suggest vitamin D dose-dependent differential expression of miRNAs target key signaling pathways of the pathogenesis of dengue disease.

scholarly journals VITAMIN D PROMOTES PROTEIN HOMEOSTASIS AND LONGEVITY VIA STRESS RESPONSE GENES SKN-1, IRE-1, AND XBP-1

2017 ◽  
Vol 1 (suppl_1) ◽  
pp. 1223-1223
Author(s):  
K.J. Dumas ◽  
K.A. Mark ◽  
D. Bhaumik ◽  
S. Davis ◽  
R. Brem ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stress Response ◽  
Protein Homeostasis ◽  
Stress Response Genes

scholarly journals Down Regulation Of IL-1β Secretion By Tgf-β1 In Macrophages Infected With Dengue Virus

2021 ◽  
Author(s):  
Brenda Ramírez-Aguero ◽  
Javier Serrato-Salas ◽  
José Luis Montiel-Hernández ◽  
Judith González-Christen
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Inflammatory Cytokines ◽  
Denv Infection ◽  
Inhibitory Effect ◽  
Microvascular Endothelium ◽  
Infected Cells ◽  
Tgf Β1 ◽  
Pro Inflammatory Cytokines

AbstractSeveral pathogenic mechanisms have been linked to the severity of dengue virus infection, like viral cytotoxicity, underlying host genetics and comorbidities such as diabetes and dyslipidemia. It has been observed that patients with severe manifestations develop an uncontrolled immune response, with an increase in pro-inflammatory cytokines such as TNF, IL-1β, IL-8, IL-6 and chemokines that damage the human microvascular endothelium, and also in anti-inflammatory cytokines IL-4, IL-10 and TGF-β1. The role of TGF-β1 on dengue is not clear; few studies have been published, and most of them from patient sera data, with both protective and pathological roles have described. The aim of this study was to evaluate the ability of TGF-β1 to regulate the secretion of IL-1β in macrophages infected by DENV using THP-1 cells treated with recombinant TGF-β1 before or after DENV infection. By RT-PCR we did not observe a difference in IL-1β expression between infected cells pretreated with TGF-β1 and those that were not. However, secretion of IL-1β was reduced only in cells stimulated with TGF-β1 before infection, and not in those treated 2 hours post-infection. TGF-β1 receptor blockage with SB505124 inhibitor, prior to the addition of TGF-β1 and infection, abrogated the inhibitory effect of TGF-β1. Our results suggest that DENV could regulate the function of TGF-β1 on macrophages. This negative regulation of the TGF-β1 pathway could be used by DENV to evade the immune response and could contribute to the immunopathology.

scholarly journals Comparison of miRNA expression profiles in pituitary–adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1682 ◽  
Author(s):  
Wei Luo ◽  
Meixia Fang ◽  
Haiping Xu ◽  
Huijie Xing ◽  
Jiangnan Fu ◽  
...  
Keyword(s):  
Stress Response ◽  
Adrenal Cortex ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Mirna Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Stress Exposure ◽  
Mirna Expression Profiles ◽  
Pituitary Adrenal Axis

MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus–pituitary–adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 &p-value < 0.001), that shared in at least two pituitary comparisons and at least two adrenal cortex comparisons, were detected separately. These identified DE-miRNAs were predicted for target genes, thus resulting in 3,959 and 4,010 target genes in pituitary and adrenal cortex, respectively. Further, 105 and 10 differentially expressed genes (DEGs) (Fold change > 2 &p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulatingMMDin pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its feasible role in regulating chronic stress in the pituitary and hippocampus through targetingMMD.

scholarly journals Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Erick X. Pérez-Guzmán ◽  
Petraleigh Pantoja ◽  
Crisanta Serrano-Collazo ◽  
Mariah A. Hassert ◽  
Alexandra Ortiz-Rosa ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Dengue Virus ◽  
T Cell Responses ◽  
Denv Infection ◽  
Zikv Infection ◽  
Cell Responses ◽  
Inflammatory Status ◽  
Short Period ◽  
The Impact

Abstract Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

scholarly journals Nuclear dengue virus NS5 antagonizes expression of PAF1-dependent immune response genes

2021 ◽  
Author(s):  
Marine J Petit ◽  
Matthew W Kenaston ◽  
Ariana A Nagainis ◽  
Priya S Shah
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Protein Interaction ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Close Association ◽  
Gene Expression Profiles ◽  
Structural Protein ◽  
Immune Response Genes ◽  
Viral Determinants

Dengue virus (DENV) disruption of the innate immune response is critical to establish infection. DENV non-structural protein 5 (NS5) plays a central role in this disruption, such as antagonism of STAT2. We recently found that DENV serotype 2 (DENV2) NS5 interacts with Polymerase associated factor 1 complex (PAF1C). The primary members of PAF1C are PAF1, LEO1, CTR9 and CDC73. This nuclear complex is an emerging player in the immune response. It promotes the expression of many genes, including genes related to the antiviral, antimicrobial and inflammatory responses, through close association with the chromatin of these genes. Our previous work demonstrated that NS5 antagonizes PAF1C recruitment to immune response genes. However, it remains unknown if NS5 antagonism of PAF1C is complementary to its antagonism of STAT2. Here, we show that knockout of PAF1 enhances DENV2 infectious virion production. By comparing gene expression profiles in PAF1 and STAT2 knockout cells, we find that PAF1 is necessary to express immune response genes that are STAT2-independent. Finally, we mapped the viral determinants for the NS5-PAF1C protein interaction. We found that NS5 nuclear localization and the C-terminal region of the methyltransferase domain are required for its interaction with PAF1C. Mutation of these regions rescued the expression of PAF1-dependent immune response genes that are antagonized by NS5. In sum, our results support a role for PAF1C in restricting DENV2 replication that NS5 antagonizes through its protein interaction with PAF1C.

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