Respiratory syncytial virus (RSV) induces pathogenic syncytia through its fusion (F) protein, but the way it orchestrates fusion throughout the crowded plasma membrane stays unclear. By integrating live-cell and super-resolution microscopy, we visualized the spatiotemporal dynamics of RSV F from secretion to membrane meeting. We present RSV F effectively traffics to the plasma membrane and triggers F-actin-enriched protrusions that facilitate fusion, depending on branched actin reworking. Superresolution imaging additional reveals that RSV F reorganizes from nanoscale clusters into near-continuous ribbon-like nanodomains at cell-cell contacts, forming a secure fusion platform. This work instantly visualizes the actin-driven nanoscale meeting of a viral fusogen, defining a key mechanism in RSV pathogenesis and revealing a nanoscale goal for antiviral intervention, thereby underscoring the facility of superior nanoscopy to unravel complicated host-pathogen interactions on the molecular degree.
