ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
This article is part of the Research TopicIntegrated Genomic and Systems Approaches to Unravel Host-Virus Interactions in Viral Infectious DiseasesView all 4 articles
Study on Spatiotemporal Regulation of Interferon-Stimulated Genes during Zika Virus Infection
Provisionally accepted
- 1Army Medical University, Chongqing, China
- 2army mdeical univeristy, chongqing, China
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Zika virus (ZIKV) can cause severe neurological disorders such as congenital microcephaly, and there are currently no approved prevention or treatment measures. Elucidating the antiviral mechanism of host interferon-stimulated genes (ISGs) is crucial for developing therapeutic strategies. This study integrated multi-system transcriptomic data (human brain organoids, monocyte-derived dendritic cells (moDCs), and peripheral blood mononuclear cells (PBMCs) from infected patients), combined with cellular experiments and bioinformatics analysis, to systematically investigate the spatiotemporal regulation characteristics and functions of ISGs during ZIKV infection. Results showed that IFN-β treatment significantly activated ISGs (e.g., IRF7, IFITM3) in ZIKV-infected brain organoids, which were enriched in virus defense-related pathways. Single-cell transcriptomics revealed cellular heterogeneity in IFN-β-driven ISGs responses in moDCs. Transcriptomic analysis of PBMCs identified 210 differentially expressed genes between the acute and convalescent phases; core ISGs (e.g., RSAD2, OAS3) were transiently upregulated in the acute phase and shared some immune pathways with other viral infections.Through cross-analysis, 22 cross-system shared ISGs were screened out. LASSO regression identified 11 potential diagnostic biomarkers for ZIKV infection. siRNA knockdown experiments confirmed that IFI35, IFI44, and OAS3 exerted antiviral effects by inhibiting ZIKV replication. This study reveals the functional plasticity of ISGs and provides key targets and theoretical support for ZIKV prevention and treatment.
Keywords: biomarkers, brain organoids, Interferon signaling pathway, interferon-stimulated genes (ISGs), single-cell RNA sequencing, Transcriptomics, Zika virus (ZIKV)
Received: 09 Sep 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Chen, Gong, Guo, He, Yang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jintao Li
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