美国基因泰克公司Claudio Ciferri等研究人员合作揭示人类巨细胞病毒（HCMV）的三聚体结构，从而揭示受体识别和细胞进入的基础。2021年2月23日，《细胞》杂志在线发表了这项成果。

研究人员表示，HCMV感染了大多数人，并且是导致先天性出生缺陷的主要病毒原因。HCMV利用糖蛋白gHgLgO（三聚体）与血小板衍生的生长因子受体α（PDGFRα）结合并转化生长因子β受体3（TGFβR3）进入多种细胞类型。该复合物被有效的中和抗体靶向，并且是HCMV的治疗剂的重要候选靶点。

研究人员确定了三聚体的三种冷冻电镜（cryo-EM）结构及其与四个结合蛋白的相互作用细节：受体蛋白PDGFRα和TGFβR3以及两种广泛中和的抗体。三聚体与PDGFRα和TGFβR3的结合是互斥的，表明它们起独立的进入受体的作用。另外，三聚体-PDGFRα相互作用对PDGFRα信号传导具有抑制作用。

这些结果为理解HCMV受体的参与、中和以及针对HCMV的抗病毒策略开发提供了框架。 

附：英文原文

Title: Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry

Author: Marc Kschonsak, Lionel Rougé, Christopher P. Arthur, Ho Hoangdung, Nidhi Patel, Ingrid Kim, Matthew C. Johnson, Edward Kraft, Alexis L. Rohou, Avinash Gill, Nadia Martinez-Martin, Jian Payandeh, Claudio Ciferri

Issue&Volume: 2021-02-23

Abstract: Human cytomegalovirus (HCMV) infects the majority of the human population and representsthe leading viral cause of congenital birth defects. HCMV utilizes the glycoproteinsgHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRα)and transforming growth factor beta receptor 3 (TGFβR3) to gain entry into multiplecell types. This complex is targeted by potent neutralizing antibodies and representsan important candidate for therapeutics against HCMV. Here, we determine three cryogenicelectron microscopy (cryo-EM) structures of the trimer and the details of its interactionswith four binding partners: the receptor proteins PDGFRα and TGFβR3 as well as twobroadly neutralizing antibodies. Trimer binding to PDGFRα and TGFβR3 is mutually exclusive,suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRαinteraction has an inhibitory effect on PDGFRα signaling. Our results provide a frameworkfor understanding HCMV receptor engagement, neutralization, and the development ofanti-viral strategies against HCMV.

DOI: 10.1016/j.cell.2021.01.036

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00079-9