Entry of Enveloped Viruses into Host Cells: Membrane Fusion

Viruses are intracellular parasites that hijack the cellular machinery for their own replication. Therefore, an obligatory step in the virus life cycle is the delivery of the viral genome inside the cell. Enveloped viruses (i.e., viruses with a lipid envelope) use a two-step procedure to release their genetic material into the cell: (1) they first bind to specific surface receptors of the target cell membrane and then (2) they fuse the viral and cell membranes. This last step may occur at the cell surface or after internalization of the virus particle by endocytosis or by some other route (e.g., macropinocytosis). Remarkably, the virus–cell membrane fusion process goes essentially along the same intermediate steps than other membrane fusions that occur, for instance, in vesicular fusion at the nerve synapsis or cell–cell fusion in yeast mating. Specialized viral proteins, fusogens, promote virus–cell membrane fusion. The viral fusogens experience drastic structural rearrangements during fusion, releasing the energy required to overcome the repulsive forces that prevent spontaneous fusion of the two membranes. This chapter provides an overview of the different types of viral fusogens and their mode of action, as they are currently known. Furthermore, it outlines novel strategies for vaccine development related to stabilized viral fusogens.