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DOI	10.1073/pnas.2020732118
	Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46
	David Persson B.; John L.; Rafie K.; Strebl M.; Frängsmyr L.; Ballmann M.Z.; Mindler K.; Havenga M.; Lemckert A.; Stehle T.; Carlson L.-A.; Arnberg N.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion–CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adenovirus \| hexon \| CD46 \| receptor \| vaccine
语种	英语
scopus关键词	capsid protein; fiber protein; hexon protein; membrane cofactor protein; unclassified drug; capsid protein; Article; cell assay; controlled study; cryoelectron microscopy; host cell; human; Human adenovirus B; Human adenovirus D; human adenovirus infection; human cell; nonhuman; priority journal; protein analysis; protein binding; protein domain; protein expression; protein function; protein protein interaction; surface plasmon resonance; validation process; virion; virogenesis; virus entry; virus identification; biosynthesis; cell line; gene expression regulation; genetics; Human adenovirus C; metabolism; Adenoviruses, Human; Capsid Proteins; Cell Line; COVID-19 Vaccines; Gene Expression Regulation, Viral; Humans; SARS-CoV-2; Virus Internalization
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180997
作者单位	Department of Clinical Microbiology, Division of Virology, Umeå University, Umeå, SE-90185, Sweden; Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, SE-90185, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, SE-90187, Sweden; Department of Medical Biochemistry, Umeå University, Umeå, SE-90187, Sweden; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, D-72076, Germany; Batavia Biosciences, Leiden, 2333 CL, Netherlands; National Veterinary Institute, Uppsala, SE-75189, Sweden
推荐引用方式 GB/T 7714	David Persson B.,John L.,Rafie K.,et al. Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46[J],2021,118(3).
APA	David Persson B..,John L..,Rafie K..,Strebl M..,Frängsmyr L..,...&Arnberg N..(2021).Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	David Persson B.,et al."Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).