A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic reoviruses

Abstract

The non‐enveloped fusogenic avian and Nelson Bay reoviruses encode homologous 10 kDa non‐structural transmembrane proteins. The p10 proteins localize to the cell surface of transfected cells in a type I orientation and induce efficient cell–cell fusion. Mutagenic studies revealed the importance of conserved sequence‐predicted structural motifs in the membrane association and fusogenic properties of p10. These motifs included a centrally located transmembrane domain, a conserved cytoplasmic basic region, a small hydrophobic motif in the N‐terminal domain and four conserved cysteine residues. Functional analysis indicated that the extreme C‐terminus of p10 functions in a sequence‐independent manner to effect p10 membrane localization, while the N‐terminal domain displays a sequence‐dependent effect on the fusogenic property of p10. The small size, unusual arrangement of structural motifs and lack of any homologues in previously described membrane fusion proteins suggest that the fusion‐associated small transmembrane (FAST) proteins of reovirus represent a new class of membrane fusion proteins.

Modification of Late Membrane Permeability in Avian Reovirus-infected Cells

“…All three S1 ORFs are expressed in infected cells (11,12); ORFs 1 and 2 direct the synthesis of the nonstructural proteins p10 and p17, which associate with cell membranes, whereas distal ORF3 expresses protein C, a minor trimeric structural protein that is involved in virus attachment to cell receptors (13,14). Recent evidence indicates that there is a close association between nonstructural p10 protein and the syncytial phenotype displayed by avian reoviruses (11,15). This protein is a small transmembrane type-I (N-out) protein, and mutagenic analysis revealed that a region of its extracellular NH 2 -terminal domain displays a sequence-dependent effect on the fusogenic activity of p10 (Ref.…”

Identification of a functional motif in the AqRV NS26 protein required for enhancing the fusogenic activity of FAST protein NS16

“…In addition, our recent studies on the nonstructural protein NS16 have proved that the NS16 protein is a fusion-associated small transmembrane (FAST) protein and can induce cell-cell fusion in transfected cells . However, unlike the efficient cell-cell fusion mediated by orthoreovirus FAST proteins (p10, p14 and p15) (Corcoran & Duncan, 2004;Dawe & Duncan, 2002;Shmulevitz & Duncan, 2000), the fusion activity of AqRV NS16 in transfected cells is relatively weak .…”

Cell-Cell Membrane Fusion Induced by p15 Fusion-associated Small Transmembrane (FAST) Protein Requires a Novel Fusion Peptide Motif Containing a Myristoylated Polyproline Type II Helix

“…Unlike the enveloped virus fusogens, the FAST proteins are nonstructural viral proteins that are expressed inside virus-infected cells where they traffic to the plasma membrane to induce fusion of virus-infected cells with neighboring uninfected cells (5,7). The FAST proteins have therefore specifically evolved to induce cell-cell, rather than virus-cell, membrane fusion.…”