从识别到执行——CMV 五聚体从受体结合到融合触发。

From recognition to execution-the HCMV Pentamer from receptor binding to fusion triggering.

机构信息

GSK, 14200 Shady Grove Road, Rockville, MD 20850, USA.

Moderna, 500 Technology Square, Cambridge, MA 02139, USA.

出版信息

Curr Opin Virol. 2018 Aug;31:43-51. doi: 10.1016/j.coviro.2018.05.004. Epub 2018 Jun 1.

DOI:10.1016/j.coviro.2018.05.004

PMID:29866439

Abstract

The β-herpesvirus human cytomegalovirus (HCMV) is the leading viral cause of neonatal developmental disabilities. In HCMV, the conserved herpesvirus glycoprotein B (gB) mediates membrane fusion between the viral and host cell membranes, whereas the trimeric gH/gL/gO or the pentameric gH/gL/UL128/UL130/UL31A complexes (Pentamer) bind to cell-specific receptors and provide the triggering signal to gB. Recent structural and functional studies have provided new insights into Pentamer structure, conformational flexibility, location of epitopes for neutralizing antibodies and potential binding sites for cell surface receptors. Together, these data suggest a model where receptor binding triggers a conformational change in Pentamer, allowing it to interact with gB and initiate the membrane fusion process.

摘要

β-疱疹病毒人巨细胞病毒（HCMV）是导致新生儿发育障碍的主要病毒病原体。在 HCMV 中，保守的疱疹病毒糖蛋白 B（gB）介导病毒和宿主细胞膜之间的膜融合，而三聚体 gH/gL/gO 或五聚体 gH/gL/UL128/UL130/UL31A 复合物（五聚体）结合到细胞特异性受体上，并为 gB 提供触发信号。最近的结构和功能研究为五聚体结构、构象灵活性、中和抗体表位的位置以及潜在的细胞表面受体结合位点提供了新的见解。这些数据共同表明，受体结合触发五聚体构象变化，使其能够与 gB 相互作用并启动膜融合过程。