Membrane fusion mechanisms: The influenza hemagglutinin paradigm and its implications for intracellular fusion

The mechanism of membrane fusion induced by the influenza virus hemagglutin in (HA) has been extensively characterized. Fusion is triggered by low pH, which induces conformational changes in the protein, leading to insertion o f a hydrophobic 'fusion peptide' into the viral membrane and the target mem brane for fusion. Insertion perturbs the target membrane, and hour glass-sh aped lipidic fusion intermediates, called stalks, fusing the outer monolaye rs of the two membranes, are formed. Stalk formation is followed by complet e fusion of the two membranes. Structures similar to those formed by HA at the pH of fusion are found not only in many other viral fusion proteins, bu t are also formed by SNAREs, proteins involved in intracellular fusion. Sub stances that inhibit or promote HA-induced fusion because they affect stalk formation, also inhibit or promote intracellular fusion, cell-cell fusion and even in intracellular fission similarly. Therefore, the mechanism of in fluenza HA-induced fusion may be a paradigm for many intracellular fusion e vents.