ArticleThe Journal of biological chemistry2011
Mutagenesis of surfactant protein D informed by evolution and x-ray crystallography enhances defenses against influenza A virus in vivo.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Investigating the structural basis of surfactant protein D oligomerization: The crucial role of Cys15-Cys15/Cys20-Cys20 disulfide bond linkage.Protein science : a publication of the Protein Society · 2026Article
- Multivalent interactions between fully glycosylated influenza virus hemagglutinins mediated by glycans at distinct N-glycosylation sites.Npj viruses · 2024Article
- Glycosylation of H4 influenza strains with pandemic potential and susceptibilities to lung surfactant SP-D.Frontiers in molecular biosciences · 2023Article
- Elucidating the enhanced binding affinity of a double mutant SP-D with trimannose on the influenza A virus using molecular dynamics.Computational and structural biotechnology journal · 2022Article
- Article
- Viral Evasion of Innate Immune Defense: The Case of Resistance of Pandemic H1N1 Influenza A Virus to Human Mannose-Binding Proteins.Frontiers in microbiology · 2021Article
- Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D:Journal of virology · 2020Article
- Innate Immunity and Influenza A Virus Pathogenesis: Lessons for COVID-19.Frontiers in cellular and infection microbiology · 2020Review
- Why Glycosylation Matters in Building a Better Flu Vaccine.Molecular & cellular proteomics : MCP · 2019Review
- All-Atom Molecular Dynamics Simulations of Dimeric Lung Surfactant Protein B in Lipid Multilayers.International journal of molecular sciences · 2019Article
- Influenza virus N-linked glycosylation and innate immunity.Bioscience reports · 2019Review
- Enhanced Antiviral Activity of Human Surfactant Protein D by Site-Specific Engineering of the Carbohydrate Recognition Domain.Frontiers in immunology · 2019Article
- Surfactant Proteins A and D: Trimerized Innate Immunity Proteins with an Affinity for Viral Fusion Proteins.Journal of innate immunity · 2019Review
- Lectin-mediated binding and sialoglycans of porcine surfactant protein D synergistically neutralize influenza A virus.The Journal of biological chemistry · 2018Article
- The Role and Molecular Mechanism of Action of Surfactant Protein D in Innate Host Defense Against Influenza A Virus.Frontiers in immunology · 2018Review
- Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A review of methods for interpretation of glycopeptide tandem mass spectral data.Glycoconjugate journal · 2016Review
- Integrated Omics and Computational Glycobiology Reveal Structural Basis for Influenza A Virus Glycan Microheterogeneity and Host Interactions.Molecular & cellular proteomics : MCP · 2016Article
- Human lectins and their roles in viral infections.Molecules (Basel, Switzerland) · 2015Review
- Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses.American journal of physiology. Lung cellular and molecular physiology · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The recognition of influenza A virus (IAV) by surfactant protein D (SP-D) is mediated by interactions between the SP-D carbohydrate recognition domains (CRD) and glycans displayed on envelope glycoproteins. Although native human SP-D shows potent antiviral and aggregating activity, trimeric recombinant neck+CRDs (NCRDs) show little or no capacity to influence IAV infection. A mutant trimeric NCRD, D325A/R343V, showed marked hemagglutination inhibition and viral neutralization, with viral aggregation and aggregation-dependent viral uptake by neutrophils. D325A/R343V exhibited glucose-sensitive binding to Phil82 hemagglutinin trimer (HA) by surface plasmon resonance. By contrast, there was very low binding to the HA trimer from another virus (PR8) that lacks glycans on the HA head. Mass spectrometry demonstrated the presence of high mannose glycans on the Phil82 HA at positions known to contribute to IAV binding. Molecular modeling predicted an enhanced capacity for bridging interactions between HA glycans and D325A/R343V. Finally, the trimeric D325A/R343V NCRD decreased morbidity and increased viral clearance in a murine model of IAV infection using a reassortant A/WSN/33 virus with a more heavily glycosylated HA. The combined data support a model in which altered binding by a truncated mutant SP-D to IAV HA glycans facilitates viral aggregation, leading to significant viral neutralization in vitro and in vivo. These studies demonstrate the potential utility of homology modeling and protein structure analysis for engineering effective collectin antivirals as in vivo therapeutics.
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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.