The Reovirus Fusion-Associated Small Transmembrane (FAST) Proteins: Virus-Encoded Cellular Fusogens

This chapter discusses the current understanding of fusion-associated small transmembrane (FAST) protein structure–function relationships and how these remarkable viral fusogens mediate cell–cell fusion and syncytium formation. The reovirus FAST proteins are a singular family of viral membrane fusion proteins that function as dedicated cell–cell fusogens. Each of the FAST proteins contains a unique repertoire and arrangement of functional motifs, assembled into three small fusion modules (the ectodomain, transmembrane domain (TMD), and endodomain). These fusion modules are interchangeable, but specific combinations of membrane interaction motifs are required to generate a functional fusogen, implying the fusion modules function in a coordinated manner to induce syncytium formation. The lipid membrane that surrounds enveloped viruses is studded with multiple copies of a fusion protein complex. These fusion complexes mediate intracellular delivery of the viral genome by fusing the viral membrane with a cellular membrane. Enveloped viruses that assemble by budding through the plasma membrane localize their fusion proteins on the cell surface, which can result in cell–cell fusion and syncytium formation and contribute to the pathogenic potential of these enveloped viruses.