Proteomic Analysis of Virus-Host Interactions in an Infectious Context Using Recombinant

RNA viruses exhibit small-sized genomes encoding few proteins, but still establish complex networks of interac-tions with host cell components to achieve replication and spreading. Ideally, these virus-host protein interactions should be mapped directly in infected cell culture, but such a high standard is often difficult to reach when using conventional approaches. We thus developed a new strat-egy based on recombinant viruses expressing tagged vi-ral proteins to capture both direct and indirect physical binding partners during infection. As a proof of concept, we engineered a recombinant measles virus (MV) ex-pressing one of its virulence factors, the MV-V protein, with a One-STrEP amino-terminal tag. This allowed virus-host protein complex analysis directly from infected cells by combining modified tandem affinity chromatograph