ArticleJournal of virology2015
Identification and mutagenesis of the adeno-associated virus 5 sialic acid binding region.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
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- The Structural, Biophysical, and Antigenic Characterization of the Goose Parvovirus Capsid.Microorganisms · 2025Article
- Distinct infectivity and neutralization antibody responses in the highly homologous AAV Go.1 and AAV5.Frontiers in medicine · 2025Article
- Structural Characterization of Human Bufavirus 1: Receptor Binding and Endosomal pH-Induced Changes.Viruses · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
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- Prophylactic Prednisolone Promotes AAV5 Hepatocyte Transduction Through the Novel Mechanism of AAV5 Coreceptor Platelet-Derived Growth Factor Receptor Alpha Upregulation and Innate Immune Suppression.Human gene therapy · 2024Article
- Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium.Journal of virology · 2023Article
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- Bipartite genome and structural organization of the parvovirus Acheta domesticus segmented densovirus.Nature communications · 2023Article
- Biophysical characterization of adeno-associated virus capsid through the viral transduction life cycle.Journal, genetic engineering & biotechnology · 2023Review
- Adeno-associated virus receptor complexes and implications for adeno-associated virus immune neutralization.Frontiers in microbiology · 2023Article
- Cross-Species Permissivity: Structure of a Goat Adeno-Associated Virus and Its Complex with the Human Receptor AAVR.Journal of virology · 2022Article
- Cryo-electron Microscopy of Adeno-associated Virus.Chemical reviews · 2022Review
- Directed evolution of adeno-associated virus 5 capsid enables specific liver tropism.Molecular therapy. Nucleic acids · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledAs a genus, the dependoviruses use a diverse group of cell surface carbohydrates for attachment and entry. Despite the fact that a majority of adeno-associated viruses (AAVs) utilize sialic acid (SIA) for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, two SIA binding regions were mapped for AAV5. The first site mapped to the depression in the center of the 3-fold axis of symmetry, while the second site was located under the βHI loop close to the 5-fold axis. Mutagenesis of amino acids 569 and 585 or 587 within the 3-fold depression resulted in elimination or alteration in SIA-dependent transduction, respectively. This change in SIA binding was confirmed using glycan microarrays. Mutagenesis of the second site identified a role in transduction that was SIA independent. Further studies of the mutants at the 3-fold site demonstrated a change in transduction activity and cell tropism in vivo as well as resistance to neutralization by a polyclonal antibody raised against the wild-type virus. IMPORTANCE: Despite the fact that a majority of AAVs utilize sialic acid for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, the sialic acid binding regions of AAV5 were identified and studied using a variety of approaches. Mutagenesis of this region resulted in elimination or alteration in sialic acid-dependent transduction in cell lines. This change in sialic acid glycan binding was confirmed using glycan arrays. Further study also demonstrated a change in transduction and activity and cell tropism in vivo as well as resistance to neutralization by antibodies raised against the wild-type virus.
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Registered trials
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.