Hendra virus is a highly pathogenic paramyxovirus classified as a biosafety 
level four agent. The fusion (F) protein of Hendra virus is critical for 
promoting viral entry and cell-to-cell fusion. To be fusogenically active, 
Hendra virus F must undergo endocytic recycling and cleavage by the 
endosomal/lysosomal protease cathepsin L, but the route of Hendra virus F 
following internalization and the recycling signals involved are poorly 
understood. We examined the intracellular distribution of Hendra virus F 
following endocytosis and showed that it is primarily present in Rab5- and 
Rab4-positive endosomal compartments, suggesting that cathepsin L cleavage 
occurs in early endosomes. Hendra virus F transmembrane domain (TMD) residues 
S490 and Y498 were found to be important for correct Hendra virus F recycling, 
with the hydroxyl group of S490 and the aromatic ring of Y498 important for this 
process. In addition, changes in association of isolated Hendra virus F TMDs 
correlated with alterations to Hendra virus F recycling, suggesting that 
appropriate TMD interactions play an important role in endocytic trafficking.