ArticlePloS one2011
Cell entry and trafficking of human adenovirus bound to blood factor X is determined by the fiber serotype and not hexon:heparan sulfate interaction.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Development of adenoviral vectors that transduce Purkinje cells and other cerebellar cell-types in the cerebellum of a humanized mouse model.Molecular therapy. Methods & clinical development · 2024Article
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- Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction.Viruses · 2022Article
- In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells.Biomedicines · 2022Article
- Article
- Safe and efficientMolecular therapy. Methods & clinical development · 2022Article
- The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal.Pharmaceutics · 2021Review
- Designer Oncolytic Adenovirus: Coming of Age.Cancers · 2018Review
- Blood Coagulation Factor X Exerts Differential Effects on Adenovirus Entry into Human Lymphocytes.Viruses · 2018Article
- A comparative review of viral entry and attachment during large and giant dsDNA virus infections.Archives of virology · 2017Review
- Evaluation of CD46 re-targeted adenoviral vectors for clinical ovarian cancer intraperitoneal therapy.Cancer gene therapy · 2016Article
- The Use of Adenovirus Dodecahedron in the Delivery of an Enzymatic Activity in the Cell.Biotechnology research international · 2016Article
- Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications.Viruses · 2015Review
- Hexon hypervariable region-modified adenovirus type 5 (Ad5) vectors display reduced hepatotoxicity but induce T lymphocyte phenotypes similar to Ad5 vectors.Clinical and vaccine immunology : CVI · 2014Article
- Human full-length coagulation factor X and a GLA domain-derived 40-mer polypeptide bind to different regions of the adenovirus serotype 5 hexon capsomer.Human gene therapy · 2014Article
- A myeloid cell-binding adenovirus efficiently targets gene transfer to the lung and escapes liver tropism.Gene therapy · 2013Article
- Mutation of the fiber shaft heparan sulphate binding site of a 5/3 chimeric adenovirus reduces liver tropism.PloS one · 2013Article
- Article
- Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells.Journal of virology · 2011Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human adenovirus serotype 5 (HAdV5)-based vectors administered intravenously accumulate in the liver as the result of their direct binding to blood coagulation factor X (FX) and subsequent interaction of the FX-HAdV5 complex with heparan sulfate proteoglycan (HSPG) at the surface of liver cells. Intriguingly, the serotype 35 fiber-pseudotyped vector HAdV5F35 has liver transduction efficiencies 4-logs lower than HAdV5, even though both vectors carry the same hexon capsomeres. In order to reconcile this apparent paradox, we investigated the possible role of other viral capsid proteins on the FX/HSPG-mediated cellular uptake of HAdV5-based vectors. Using CAR- and CD46-negative CHO cells varying in HSPG expression, we confirmed that FX bound to serotype 5 hexon protein and to HAdV5 and HAdV5F35 virions via its Gla-domain, and enhanced the binding of both vectors to surface-immobilized hypersulfated heparin and cellular HSPG. Using penton mutants, we found that the positive effect of FX on HAdV5 binding to HSPG and cell transduction did not depend on the penton base RGD and fiber shaft KKTK motifs. However, we found that FX had no enhancing effect on the HAdV5F35-mediated cell transduction, but a negative effect which did not involve the cell attachment or endocytic step, but the intracellular trafficking and nuclear import of the FX-HAdV5F35 complex. By cellular imaging, HAdV5F35 particles were observed to accumulate in the late endosomal compartment, and were released in significant amounts into the extracellular medium via exocytosis. We showed that the stability of serotype 5 hexon:FX interaction was higher at low pH compared to neutral pH, which could account for the retention of FX-HAdV5F35 complexes in the late endosomes. Our results suggested that, despite the high affinity interaction of hexon capsomeres to FX and cell surface HSPG, the adenoviral fiber acted as the dominant determinant of the internalization and trafficking pathway of HAdV5-based vectors.
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