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Membrane Fusion

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In the case of enveloped viruses, fusion between viral and cellular membranes must occur to deliver the viral nucleic acid into the cell. Membrane fusion takes place during many cellular processes, such as cell division, myoblast fusion, and exocytosis, and must be regulated in order to maintain the integrity of the cell and its intracellular compartments. Consequently, membrane fusion proceeds by specialized mechanisms mediated by proteins and requires energy. Some of the best-characterized fusion machines are viral envelope glycoproteins.

Envelope glycoproteins from different virus families appear utterly dissimilar in primary amino acid sequence and domain organization, structure, and even function. Receptor binding and fusion of some virus particles are mediated by the same protein. For others, these functions are segregated into two distinct proteins. Some viral proteins can mediate fusion at the cell surface, while others require activation by acidic pH in endocytic vesicles. Nevertheless, despite these differences, the fusion mechanism is remarkably similar between all fusion proteins from different virus families and relies on conformational changes in the viral protein or subunit that mediates fusion. Based on protein structure, viral fusion proteins can be assigned to one of three classes. Class I includes the most extensively studied examples of fusion proteins, exemplified by influenza virus HA. The study of this protein elucidated the mechanism of fusion with general features that are common to all fusion proteins regardless of class.

Principles of Virology

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