IFITM1-mediated restriction of henipavirus entry is associated with ephrinB2 reorganization and confinement in membrane nanodomains.

IFITM1 restricts Nipah and Hendra virus entry by enlarging IFITM1 nanoclusters and reorganizing ephrinB2 into denser membrane-domain clusters, linked to confined ephrinB2 diffusion.

• Why it matters: IFITM proteins block many viruses at entry, but how IFITM1 shapes henipavirus receptor behavior at the plasma membrane is unclear.
• What they did: In human epithelial and endothelial cells, IFITM1 knockdown enhanced and IFITM1 overexpression inhibited HNV entry and cell-cell fusion; single-molecule localization and single-particle tracking mapped IFITM1, GM1 raft-like domains, and ephrinB2.
• The result: EphrinB2 formed larger, denser clusters with IFITM1 and its lateral diffusion became confined, changes not reversed by amphotericin B and not reversed for IFITM1-mediated NiV restriction.

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