Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor

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The fusogenic ortho- and aquareoviruses are the only known nonenveloped viruses that induce syncytium formation. Cell-cell fusion is a virulence determinant of fusogenic reoviruses, and is mediated by a singular family of fusion-associated small transmembrane (FAST) proteins, the smallest known viral fusogens. Unlike their enveloped virus counterparts, reovirus FAST proteins have exceptionally small ectodomains and considerable larger cytoplasmic endodomains, suggesting FAST protein interactions with the cytoplasmic leaflet of the plasma membrane likely play a prominent role in the fusion process. We determined that the baboon reovirus p15 FAST protein endodomain contains a novel type of helix-loop-helix lipid packing sensor that partitions into hydrophobic defects present in highly curved membranes. This fusion-inducing lipid packing sensor (FLiPS) is required for pore formation, and can be functionally replaced by heterologous lipid packing sensors. By masking hydrophobic defects appearing in the highly curved rim of nascent fusion pores, the FliPS would make the forward reaction to pore formation a more energetically favored means of resolving an unstable hemifusion intermediate. These results define a new role for curvature sensing motifs, and reveal how viral fusion proteins can drive pore formation without having to rely on membrane stresses induced by complex refolding of large ectodomains.

Vyšlo v časopise: Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004962
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004962

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