ArticlePLoS pathogens2015
Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Structural requirements of blood factors binding to soluble hexon trimers with implications for adenovirus cell targeting and immune evasion.PLoS pathogens · 2026Article
- Current use of pre-clinical models for evaluation of human adenovirus-based cancer therapeutics.Molecular therapy. Oncology · 2026Review
- Red Blood Cell-Associated Features of Adenoviral Vector-Linked Venous Thrombosis.International journal of molecular sciences · 2025Article
- Next-Generation Adenoviral Vector-Based Vaccines for Severe Acute Respiratory Syndrome Coronavirus-2.Vaccines · 2025Review
- Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.Theranostics · 2025Article
- An oncolytic HAdV-5 with reduced surface charge combines diminished toxicity and improved tumor targeting.Molecular therapy. Oncology · 2024Article
- The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine.Viruses · 2023Review
- Adenovirus entry: Stability, uncoating, and nuclear import.Molecular microbiology · 2022Review
- Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo.PLoS pathogens · 2022Article
- In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells.Biomedicines · 2022Article
- First Record of HAdV-D20 Among Keratoconjunctivitis Patients in Iraq.Reports of biochemistry & molecular biology · 2022Article
- SpeciesViruses · 2022Article
- ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome.Science advances · 2021Article
- Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties.Viruses · 2021Review
- Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5Viruses · 2021Article
- Risk Factors for the Development of Hemophagocytic Lymphohistiocytosis in Children With Severe Adenovirus Pneumonia: A Single-Center Retrospective Study.Frontiers in pediatrics · 2021Article
- Chorioallantoic Membrane Tumor Model for Evaluating Oncolytic Viruses.Human gene therapy · 2020Article
- Systemic delivery and SPECT/CT in vivo imaging ofScientific reports · 2019Article
- Human Adenovirus Serotype 5 Is Sensitive to IgM-Independent Neutralization In Vitro and In Vivo.Viruses · 2019Article
- Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions.Nature communications · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX "coating" also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.