The fusion (F) protein of simian virus 5 strain W3A induces syncytium formation independently of coexpression of the hemagglutinin-neuraminidase protein. This property call be transferred to the F protein; of strain WR by replacing the leucine at position 22 with the W3A F counterpart, proline. The resulting mutant L22P has a conformation that is distinct from that of the WR F protein. Se-L22P is a cleavage site Mutant of L22P that is cleavable only by addition of exogenous trypsin. We showed here that the cell surface-localized L22P was internalized with a t(1/2) Of 25 min and degraded in the cell, while the WR F protein was not. The cell surface-localized Se-L22P underwent a significant conformational change upon cleavage. Intriguingly, it disappeared from the cell Surface clue to its internalization, while inducing extensive syncytium formation. These results indicate that L22P may display all internalization signal during the course of fusion induction. (C) 2005 Elsevier Inc. All rights reserved.