Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA.
Viruses. 2018 Dec 11;10(12):704. doi: 10.3390/v10120704.
The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that it infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRα) were identified as receptors, respectively, for the trimeric and pentameric glycoprotein H/glycoprotein L (gH/gL) complexes that in large part govern HCMV cell tropism, while CD90 and CD147 were also found to play roles during entry. X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved. A novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/gL and gB were reported. Additional work indicates that the pentamer promotes a mode of cell-associated spread that resists antibody neutralization, as opposed to the trimeric gH/gL complex (trimer), which appears to be broadly required for the infectivity of cell-free virions. Finally, viral factors such as UL148 and US16 were identified that can influence the incorporation of the alternative gH/gL complexes into virions. We will review these advances and their implications for understanding HCMV entry and cell tropism.
过去几年，人们在了解人类巨细胞病毒（HCMV）进入其感染的广泛细胞类型和组织的机制方面取得了实质性进展。神经纤毛蛋白-2 和血小板衍生生长因子受体α（PDGFRα）分别被鉴定为三聚体和五聚体糖蛋白 H/糖蛋白 L（gH/gL）复合物的受体，这些复合物在很大程度上控制着 HCMV 的细胞嗜性，而 CD90 和 CD147 也被发现在进入过程中发挥作用。病毒近端融合蛋白 gB 和五聚体 gH/gL 复合物（五聚体）的 X 射线晶体结构已被解析。描述了一种新型病毒粒子 gH 复合物，由与 UL116 结合而不是 gL 的 gH 组成，并报告了支持 gH/gL 和 gB 之间存在稳定复合物的发现。其他研究表明，五聚体促进了一种细胞相关传播模式，这种模式能抵抗抗体中和，而不是三聚体 gH/gL 复合物（三聚体），三聚体似乎广泛需要无细胞病毒粒子的感染性。最后，鉴定出了病毒因子，如 UL148 和 US16，它们可以影响替代 gH/gL 复合物在病毒粒子中的掺入。我们将回顾这些进展及其对理解 HCMV 进入和细胞嗜性的影响。
