Avian deltacoronaviruses encode fusion-associated small transmembrane proteins that can induce syncytia formation

Abstract

Fusion-associated small transmembrane (FAST) proteins are nonstructural viral proteins that induce cell-cell fusion. FAST proteins, which previously were identified in the genomes of double-stranded RNA viruses, typically contain an acylated N-terminal ectodomain, central transmembrane domain, and C-terminal endodomain with a polybasic region. Using sequence homology and protein motif prediction, we identified accessory proteins in a subset of avian deltacoronaviruses as putative FAST proteins. Transient expression of thrush coronavirus NS7b or common moorhen coronavirus NS7a, but not night heron coronavirus NS7b, induced cell-cell fusion. Syncytia were detected in primate kidney epithelial cells or fibroblasts but not chicken embryo fibroblasts, and addition of an N-terminal FLAG peptide to the proteins ablated fusion activity. These findings suggest that multiple avian deltacoronaviruses, positive-sense RNA viruses, encode nonstructural proteins that can mediate cell-cell fusion and share features with known FAST proteins. Additional studies are needed to understand contributions of these proteins to deltacoronavirus biology.