Quantitative interactome profiling of rabies virus P-protein isoforms P1 and P3

RNA viruses must achieve complex replication and immune evasion functions using limited coding capacity. The rabies virus P protein is a multifunctional viral protein expressed in multiple isoforms via alternative translation. In this study, we investigate how structural and functional diversity arises between two isoforms—P1 (full-length) and P3 (a naturally truncated form)—and how these differences influence host protein interactions. We used GFP-tagged P1 and P3 proteins expressed in HEK293T cells to perform quantitative immunoprecipitation-mass spectrometry (IP-MS) and define isoform-specific interactomes. This dataset includes raw and processed IP-MS data for GFP-P1, GFP-P3, and GFP control (each in quadruplicate), and supports the conclusion that conformational and functional diversification of viral proteins enables expanded host interface capacity. This study provides new mechanistic insights into how viruses exploit isoform diversity and RNA-driven interactions to overcome genome limitations.