Faculty, Staff and Student Publications
Publication Date
3-21-2025
Journal
iScience
Abstract
Viral genomes encode viral transcriptional regulators (vTRs) that manipulate host gene expression to facilitate replication and evade immune detection. Nevertheless, their role in non-cancerous diseases remains largely underexplored. Here, we unveiled 268 new candidate vTRs from 14 of the 20 viral families we investigated. We mapped vTRs' genome-wide binding profiles and identified their potential human targets, which were enriched in immune-mediated pathways, neurodegenerative disorders, and cancers. Through vTR DNA-binding preference analysis, 283 virus-specific and human-like motifs were identified. Prioritized Epstein-Barr virus (EBV) vTR target genes were associated with multiple sclerosis (MS), rheumatoid arthritis, and systemic lupus erythematosus. The partitioned heritability study among 19 diseases indicated significant enrichment of these diseases in EBV vTR-binding sites, implicating EBV vTRs' roles in immune-mediated disorders. Finally, drug repurposing analysis pinpointed candidate drugs for MS, asthma, and Alzheimer disease. This study enhances our understanding of vTRs in diverse human diseases and identifies potential therapeutic targets for future investigation.
Keywords
Health sciences, Immunology, Virology
DOI
10.1016/j.isci.2025.112081
PMID
40124487
PMCID
PMC11928865
PubMedCentral® Posted Date
2-21-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Graphical Abstract
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Diseases Commons, Medical Immunology Commons, Neurosciences Commons