Viruses rely on host cells for replication, often causing cellular damage and disease. In response, hosts activate defense mechanisms, though many viruses have evolved ways to evade these responses, leading to chronic infections. Identifying host genes that viruses exploit can inform the development of antiviral therapies by targeting specific host pathways. Differential gene expression (DGE) analysis is crucial for detecting genes with altered activity during viral infections. By comparing the RNA levels across different conditions, DGE identifies differentially expressed genes (DEGs) that indicate changes in gene expression in response to infection. Functional enrichment analysis follows DEG identification, grouping DEGs into biological pathways to clarify their roles in the host response. This chapter provides a step-by-step guide for performing DGE analysis on RNA-seq data from virus-infected and uninfected samples, covering data processing, DEG identification using edgeR, and functional enrichment analysis using KEGG and Gene Ontology. The protocol supports the analysis of both in-house RNA-seq data and public datasets from NCBI GEO repository.