摘要：SummaryHighly mutable viruses evolve to evade host immunity that exerts selective pressure and adapts to viral dynamics. Here, we provide a framework for identifying key determinants of the mode and fate of viral-immune coevolution by linking molecular recognition and eco-evolutionary dynamics. We find that conservation level and initial diversity of antigen jointly determine the timing and efficacy of narrow and broad antibody responses, which in turn control the transition between viral persistence, clearance, and rebound. In particular, clearance of structurally complex antigens relies on antibody evolution in a larger antigenic space than where selection directly acts; viral rebound manifests binding-mediated feedback between ecology and rapid evolution. Finally, immune compartmentalization can slow viral escape but also delay clearance. This work suggests that flexible molecular binding allows a plastic phenotype that exploits potentiating neutral variations outside direct contact, opening new and shorter paths toward highly adaptable states.Graphical abstractDisplay OmittedHighlights•A scale-crossing framework identifies key determinants of viral-immune coevolution•Fast specific response influences slow broad response by shaping antigen dynamics•Antibody footprint shift enables breadth acquisition and viral clearance•Model explains divergent kinetics and outcomes of HCV infection in humansBiological sciences; Immunology; Immune system evolution; Microbiology; Evolutionary processes; Mathematical biosciences
