Cleavage of the syncytial protein of J paramyxovirus is required for its ability to promote cell-cell fusion

• 成果类型: Article
• 署名作者: An, Dong; Li, Zhuo; Beavis, Ashley C.; Briggs, Kelsey R.; Harvill, Mason; He, Biao
• 署名单位: University System of Georgia; University of Georgia
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9101
• DOI: 10.1073/pnas.2403389121
• 发表日期: 2024-06-11
• 关键词: membrane-fusion; beilong-virus; hemagglutinin; hemifusion; mechanisms; proteases; genome; serine; entry; hn

摘要

Cell-cell fusion mediated by most paramyxovirus requires fusion protein (F) and attachment protein (H, HN, or G). The F protein is proteolytic cleaved to be fusogenically active. J paramyxovirus (JPV) has a unique feature in the family Paramyxoviridae: It encodes an integral membrane protein, syncytial protein (SP, formerly known as transmembrane protein, TM), which is essential in JPV- promoted cell-cell fusion (i.e., syncytial). In this study, we report that cleavage of SP is essential for its syncytial- promoting activity. We have identified the cleavage site of SP at amino acid residues 172 to 175, LKTG, and deletion of the LKTG residues abolished SP protein cleavage and its ability to promote cell-cell fusion. Replacing the cleavage site LKTG with a factor Xa protease cleavage site allows cleavage of the SP with factor Xa protease and restores its ability to promote cell-cell fusion. Furthermore, results from a hemifusion assay indicate that cleavage of SP plays an important role in the progression from the intermediate hemifusion state to a complete fusion. This work indicates that SP has many characteristics of a fusion protein. We propose that SP is likely a cell-cell fusion-promoting protein.