Parainfluenza virus 5 fusion protein maintains pre-fusion stability but not fusogenic activity following mutation of a transmembrane leucine/isoleucine domain.

The paramyxoviruses Hendra virus (HeV) and parainfluenza virus 5 (PIV5) require the fusion (F) protein to efficiently infect cells. For fusion to occur, F undergoes dramatic, essentially irreversible conformational changes to merge the viral and cell membranes into a continuous bilayer. Recently, a transmembrane (TM) domain leucine/isoleucine (L/I) zipper was shown to be critical in maintaining the expression, stability and pre-fusion conformation of HeV F, allowing for fine-tuned timing of membrane fusion. To analyse the effect of the TM domain L/I zipper in another paramyxovirus, we created alanine mutations to the TM domain of PIV5 F, a paramyxovirus model system. Our data show that while the PIV5 F TM L/I zipper does not significantly affect total expression and only modestly affects surface expression and pre-fusion stability, it is critical for fusogenic activity. These results suggest that the roles of TM L/I zipper motifs differ among members of the family Paramyxoviridae.