Department of Pediatrics, Vanderbilt University Medical Center, 2200 Children's Way, Suite 2404, Nashville, TN, 37232, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Medical Center North, 1161 21st Ave. South, Suite D-2220, Nashville, TN, 37232, USA.
Virology. 2024 Dec;600:110258. doi: 10.1016/j.virol.2024.110258. Epub 2024 Oct 9.
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.
融合相关的小跨膜(FAST)蛋白是非结构病毒蛋白,可诱导细胞-细胞融合。FAST 蛋白先前在双链 RNA 病毒的基因组中被鉴定出来,通常包含酰化的 N 端外显子、中央跨膜域和 C 端含多碱性区域的内显子。我们使用序列同源性和蛋白质模体预测,鉴定出一组禽德尔塔冠状病毒中的辅助蛋白为推定的 FAST 蛋白。雏鹅冠状病毒 NS7a 或普通黑水鸡冠状病毒 NS7a 的瞬时表达,但不是夜鹭冠状病毒 NS7b 的表达,可诱导细胞-细胞融合。在灵长类肾上皮细胞或成纤维细胞中检测到合胞体,但在鸡胚成纤维细胞中未检测到,并且在蛋白的 N 端添加 FLAG 肽可使融合活性丧失。这些发现表明,多种正链 RNA 病毒的禽德尔塔冠状病毒编码可介导细胞-细胞融合的非结构蛋白,并且与已知的 FAST 蛋白具有相似的特征。需要进一步研究这些蛋白对德尔塔冠状病毒生物学的贡献。