Influenza Fusion Mechanism Figure 1. Standard stalk-hemifusion pathway (cross-section, side-view): The initial stalk (I) radially expands (II) forming an H- shaped hemifusion diaphragm (H-HD) after the trans-leaflets (colored yellow) meet (III). When the H-HD ruptures a fusion pore is formed (IV). doi:10.1371/journal.pone.0038302.g001 however, suggest that the wild-type peptide rather stabilizes neutral to weakly positively curved membrane structures, i.e. pores and dimples but not stalks [15,21,22]. The latter would suggest that the fusion peptides do not adhere to the negatively curved circumference of the stalk, which is supported by recent molecular simulations studies [23,24]. If the peptides do not directly stabilize the stalk structure itself, it is plausible that they will promote the formation of alternate, highly stressed pre-fusion structures, such as a dimple and/or pore [6,7,16], that relax by both stabilizing and expanding the stalk in the course of fusion. Could the fusion inhibiting mutants G1V and W14A [14,25] impair the formation of a required pre-fusion structure? Is the leakage of the target membrane observed prior to lipid mixing, as induced by point mutation G13A [11], possibly related to the corrupted formation of such pre-fusion structure? Other point mutations facilitate hemifusion but selectively inhibit content mixing [11,14,15]. One of such intriguing point mutations is mutant G1S. In comparison with the wild-type, this Figure 2. A p-shaped hemifusion diaphragm (p-HD) which is generated by a stalk that has encircled a membrane pore. doi:10.1371/journal.pone.0038302.g002 PLoS ONE | www.plosone.org 2 June 2012 | Volume 7 | Issue 6 | e38302