Vitamin D Reprograms Non-Coding RNA Networks to Block Zika Virus in Human Macrophages

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Zika virus (ZIKV) infection poses risks for congenital malformations and neuroinflammatory disorders.
• Macrophages are crucial targets and reservoirs for ZIKV, mediating antiviral and inflammatory responses.
• Vitamin D (VitD) is an immunomodulator that enhances macrophage antimicrobial activity and regulates inflammation.

Purpose of the Study:

• To investigate the impact of Vitamin D on macrophage responses during ZIKV infection.
• To identify non-coding RNA (ncRNA) and mRNA networks modulated by VitD in ZIKV-infected macrophages.
• To explore potential molecular mechanisms of VitD-mediated immune regulation in ZIKV infection.

Main Methods:

• Reanalysis of publicly available RNA-seq and miRNA-seq datasets from human monocyte-derived macrophages (MDMs).
• MDMs were differentiated with or without VitD and subsequently infected with ZIKV.
• Differential expression analysis and competing endogenous RNA (ceRNA) network analysis were performed.

Main Results:

• VitD treatment significantly modulated 65 long non-coding RNAs (lncRNAs) and 23 microRNAs (miRNAs) in ZIKV-infected MDMs.
• Specific lncRNAs (e.g., HSD11B1-AS1, Lnc-FOSL2) and miRNAs (e.g., let-7a, miR-146a) were identified as potential regulators of immune and metabolic genes.
• ceRNA network analysis suggested roles for SOX2-OT and SLC9A3-AS1 in modulating immune control and viral response pathways.
• Functional enrichment analysis highlighted pathways related to metabolism, stress responses, and cell migration.

Conclusions:

• This study provides an exploratory map of ncRNA-mRNA networks influenced by VitD during ZIKV infection.
• Identified candidate molecules and pathways warrant further investigation for host-virus interactions.
• Highlights the potential of VitD in modulating macrophage responses and immune regulation against ZIKV.