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鉴定人巨细胞病毒gHgLgO三聚体是病毒体感染性的核心因素。

Identification of the human cytomegalovirus gHgLgO trimer as the central player in virion infectivity.

作者信息

Thiessen Lena, Garuti Roberto, Kubic Lucie, Kösters Miwako, Amarambedu Selvakumar Divya, Krey Thomas, Görzer Irene, Fröhlich Thomas, Adler Barbara

机构信息

Max von Pettenkofer-Institute and Gene Center, Department of Virology, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.

German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.

出版信息

PLoS Pathog. 2025 Jul 24;21(7):e1013341. doi: 10.1371/journal.ppat.1013341. eCollection 2025 Jul.

DOI:10.1371/journal.ppat.1013341
PMID:40705828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12316387/
Abstract

Glycoproteins in the viral envelope of human cytomegalovirus (HCMV) orchestrate virion tethering, receptor recognition and fusion with cellular membranes. The glycoprotein gB acts as fusion protein. The gHgL complexes gHgLgO and gHgLpUL(128,130,131A) define the HCMV cell tropism. Studies with HCMV lacking gO had indicated that gHgLgO, independently of binding to its cellular receptor PDGFRα, plays an important second role in infection. Here, we identified a gO mutation which abolished virus particle infectivity by preventing the interaction of gHgLgO with host cell heparan sulfate proteoglycans (HSPGs). We could not only show that gHgLgO - HSPG interactions are a genuine second role of gHgLgO, but also that gHgLgO is a main player in determining the infectivity of HCMV virus particles. This challenges long-accepted textbook knowledge on the role of gB and gMgN complexes in virion tethering. Additionally, it adds the gHgLgO complex to the antigens of interest for future HCMV vaccines or treatments.

摘要

人类巨细胞病毒（HCMV）病毒包膜中的糖蛋白负责协调病毒体的 tethering、受体识别以及与细胞膜的融合。糖蛋白 gB 作为融合蛋白。gHgL 复合体 gHgLgO 和 gHgLpUL(128,130,131A) 决定了 HCMV 的细胞嗜性。对缺乏 gO 的 HCMV 进行的研究表明，gHgLgO 独立于与其细胞受体 PDGFRα 的结合，在感染中发挥重要的次要作用。在这里，我们鉴定了一个 gO 突变，该突变通过阻止 gHgLgO 与宿主细胞硫酸乙酰肝素蛋白聚糖（HSPG）的相互作用而消除了病毒颗粒的感染性。我们不仅可以证明 gHgLgO - HSPG 相互作用是 gHgLgO 的真正次要作用，还可以证明 gHgLgO 是决定 HCMV 病毒颗粒感染性的主要因素。这挑战了长期以来教科书上关于 gB 和 gMgN 复合体在病毒体 tethering 中作用的知识。此外，它将 gHgLgO 复合体添加到了未来 HCMV 疫苗或治疗的感兴趣抗原中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/f4b6df05d9b5/ppat.1013341.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/83a68c277a13/ppat.1013341.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/6da89fadcebe/ppat.1013341.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/ec1a7814e7e1/ppat.1013341.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/9dcccf939e98/ppat.1013341.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/14de22dfd0db/ppat.1013341.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/f4b6df05d9b5/ppat.1013341.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/83a68c277a13/ppat.1013341.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/6da89fadcebe/ppat.1013341.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/ec1a7814e7e1/ppat.1013341.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/9dcccf939e98/ppat.1013341.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/14de22dfd0db/ppat.1013341.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4967/12316387/f4b6df05d9b5/ppat.1013341.g006.jpg

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