Exploring infection biology with mass spectrometry-based proteomics

Investigating host-pathogen interactions at the molecular level is critical for understanding infection mechanisms and identifying potential therapeutic targets. Mass spectrometry (MS)-based proteomics has rapidly become one of the most employed technique for the study of almost every aspect of the proteome, hence offering strong potential to study protein dynamics during viral infections. This review presents an overview of key MS-based approaches used in host-virus research to study changes in protein expression, cell signalling and protein-protein interactions (PPIs). For each method, we outline its underlying principles, practical and analytical expertise required and key strengths and limitations, with a particular focus on how each can be applied to study specific aspects of the dynamic interplay between host and virus. By comparing these approaches side by side, the review aims to give researchers a conceptual and practical guide on how to select the adequate MS-technique for their specific biological questions in infectious biology. Ultimately, this resource is intended to support informed experimental design in host-pathogen research, helping to harness the full potential of MS-based proteomics in uncovering the complexity of infection biology.