The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo
Open accessAbstract
Human species C adenovirus serotype 5 (Ad5) is the most common viral vector used in clinical studies worldwide. Ad5 vectors infect liver cells in vivo with high efficiency via a poorly defined mechanism, which involves virus binding to vitamin K-dependent blood coagulation factors. Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity of 229 pM. This affinity is 40-fold stronger than the reported affinity of Ad5 fiber for the cellular receptor coxsackievirus and adenovirus receptor, CAR. Cryoelectron microscopy and single-particle image reconstruction revealed that the FX attachment site is localized to the central depression at the top of the hexon trimer. Hexon-mutated virus bearing a large insertion in hexon showed markedly reduced FX binding in vitro and failed to deliver a transgene to hepatocytes in vivo . This study describes the mechanism of FX binding to Ad5 and demonstrates the critical role of hexon for virus infection of hepatocytes in vivo .
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Cites
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Adenovirus Binding to Blood Factors Results in Liver Cell Infection and Hepatotoxicity
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Adenovirus Fiber Disrupts CAR-Mediated Intercellular Adhesion Allowing Virus Escape
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Cited by
Adenoviruses: update on structure and function
Russell, W. C. (2009) · Journal of General Virology · doi:10.1099/vir.0.003087-0 · Cited by 461
Innate immunity to adenovirus: lessons from mice
Atasheva, S., Yao, J., & Shayakhmetov, D. M. (2019) · FEBS Letters · doi:10.1002/1873-3468.13696 · Cited by 87
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Metadata
- Authors
- Kalyuzhniy, O., Di Paolo, N. C., Silvestry, M., Hofherr, S. E., Barry, M. A., Stewart, P. L., & Shayakhmetov, D. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-04-08
- Volume
- 105
- Issue
- 14
- Pages
- 5483-5488
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2079523736
- Cited by
- 349
- References
- 35
- FWCI
- 23.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Kalyuzhniy, O., Di Paolo, N. C., Silvestry, M., Hofherr, S. E., Barry, M. A., Stewart, P. L., & Shayakhmetov, D. M. (2008). Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0711757105
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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