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盖特糖蛋白复合物增强了人类细胞巨核病毒进入内皮细胞的可能性

Michael J Norris^1,2, Lauren A Henderson^3,4, Mohammed N A Siddiquey³

¹Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA.

Nature microbiology

|June 30, 2025

概括

科学家们发现了一种新的人类细胞巨核病毒 (HCMV) 蛋白质复合体,即GATE复合体,它增强了病毒进入内皮细胞的速度. 这一发现为HCMV疫苗和抗病毒疗法提供了潜在的新目标.

科学领域:

病毒学病毒学
结构生物学结构生物学
免疫学免疫学免疫学

背景情况:

人类细胞巨乳病毒 (HCMV) 具有重大风险,在免疫功能低下的个体中引起出生缺陷和并发症.
了解HCMV蛋白质复合体对于开发有效的疫苗和抗病毒策略至关重要.
包括gH/gL在内的糖蛋白复合体是已知的病毒进入宿主细胞的媒介.

研究的目的:

为了识别和表征涉及病毒进入的新型HCMV蛋白质复合体.
阐明一种新发现的GH复合物的结构和功能.
探索HCMV感染的潜在治疗点.

主要方法:

在HCMV病毒上识别病毒蛋白质复合体.
低温电子显微镜 (cryo-EM) 用于确定新型复合物的结构.
分析蛋白质与蛋白质相互作用及其在病毒进入中的作用.

主要成果:

一个不同的gH复合体,称为GATE复合体,在HCMV病毒上被确定,增强了内皮细胞感染.
盖特综合体包括gH,UL116和UL141,特别是不包括gL.
低温电磁检测显示了一个约3.5 Å的结构,显示了gH支架,UL141介导的二分化,以及UL116的盖.

结论:

门综合体代表了第三个独特的病毒表面综合体,涉及HCMV细胞进入.
UL141之前以细胞内功能而闻名,在维表面复合体形成和病毒热带性中发挥作用.
盖特综合体是HCMV疫苗开发和抗病毒疗法的潜在新目标.

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