Meta-analysis of transcriptomic datasets reveals upregulated histone modification and chromatin remodeling genes in Aedes aegypti during DENV-2 infection

Background The Aedes aegypti mosquito is identified as the principal vector for several arboviruses, notably the Zika virus and dengue. Dengue, in particular, presents a substantial public health threat in regions where transmission is sustained, as well as in areas where the mosquito's adaptability and plasticity, attributed to climate change, have enabled its spread to new latitudes. While the significance of histone modifications in virus-vertebrate host interactions is well-documented, their role in virus-vector interactions remains largely unexplored. Epigenetic regulation plays a critical role in host–pathogen interactions; however, little is known about how chromatin-modifying genes respond to dengue virus serotype 2 (DENV-2) infection in Aedes aegypti . This study aimed to explore the transcriptional regulation of genes involved in histone modification and chromatin remodeling in response to DENV-2 infection, using publicly available transcriptomic datasets. Methods Four independent RNA-seq datasets were retrieved from VectorBase, corresponding to different time points post-infection (3 hpi, 18 hpi, and 14 dpi). Genes upregulated in response to infection were identified using VectorBase’s built-in search tools and GO analysis. Gene function and orthology were determined using FlyBase, OrthoDB, and DAVID. KEGG pathway enrichment was also conducted to complement functional insights. Results We identified a diverse set of upregulated genes involved in histone modification (e.g., acetyltransferases, methyltransferases, and deacetylases) and chromatin remodeling complexes (e.g., NuRD, ISWI, SWI/SNF, INO80). These genes were differentially expressed across datasets, with early upregulation observed particularly in resistant mosquito strains. Notably, at later stages of infection (14 dpi), the response was broader, suggesting a prolonged and intensified regulation of chromatin-related genes throughout the course of infection. Conclusion This is the first study to systematically integrate transcriptomic evidence for the regulation of histone modification-related genes in Aedes aegypti during DENV-2 infection. These findings highlight the potential involvement of chromatin dynamics in the mosquito’s response to viral infection and underscore the value of integrative bioinformatic approaches to explore molecular mechanisms underlying vector–pathogen interactions.