EBV-HSA-RegDB: A database of regulatory interactions between Epstein–Barr virus and human miRNAs

Abstract Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with various malignancies and autoimmune diseases. MiRNAs play crucial roles in viral-host interactions by regulating gene expression post-transcriptionally. Understanding the regulatory networks between EBV-encoded miRNAs and human miRNAs is essential for elucidating viral pathogenesis and identifying therapeutic targets. We reported the EBV-HSA miRNA Regulatory Database (EBV-HSA-RegDB, https://lbcd.ufpa.br/ebvhsa or https://lbcd.ia.br/ebvhsa ), an integrated bioinformatics resource that combines comparative sequence analysis, regulatory network reconstruction, experimental data integration, and functional gene enrichment analysis. The database incorporates miRNA sequences from miRBase, experimentally validated miRNA-target interactions from miRTarBase, transcriptomic data from cell line models, and miRNA data from ENCORI/StarBase. We implemented multiple sequence-comparison methods, including Hamming, Levenshtein similarity, and the Needleman-Wunsch alignment algorithm, to investigate miRNA seed and global alignments. The tool reconstructs and enables exploration of a comprehensive regulatory network linking experimental data on EBV-encoded miRNAs, human miRNAs, and their target genes. Gene Ontology and pathway analyses using the KEGG and Reactome databases are also available. Network analysis identified key regulatory hubs and revealed convergent targeting patterns in which EBV and human miRNAs regulate the same target genes ( IPO7 , DICER , TP53 , E2F3 , SMAD4 , SPRY2 ) and several pairs of EBV-encoded miRNAs and their human counterparts, with high similarity in their target sequences. Functional enrichment analysis uncovered significant associations with biological processes, molecular functions, cellular components, and pathways relevant to viral infection, immune response, and cellular transformation. The EBV-HSA-RegDB provides a user-friendly, interactive platform for exploring virus-host miRNA regulatory networks. This resource facilitates hypothesis generation regarding EBV pathogenesis mechanisms and may aid in elucidating novel gene targets for EBV-associated diseases.