This project presents a comprehensive, quantitative proteomics and citrullinome profiling study designed to define how viral infection remodels host protein citrullination and related cellular pathways. The experimental design integrates in vitro and in vivo models of infection, including cultured human cell lines and infected murine tissues, with parallel mock-treated or vehicle controls to enable robust comparative analyses. Proteins were labeled using a citrulline-specific chemical probe, enriched by streptavidin-based affinity purification, and processed through on-bead digestion followed by isobaric tag–based quantitative mass spectrometry to allow multiplexed comparison across biological conditions and replicates. This strategy enabled systematic identification and relative quantification of citrullinated host and viral proteins, alongside global proteome changes, while controlling for technical variability through standardized normalization and statistical workflows. The resulting dataset captures condition-specific alterations in protein modification, abundance, and functional pathways, providing a well-controlled resource for interrogating the role of post-translational modifications in viral replication, host inflammatory responses, and disease-associated molecular mechanisms.