ArticleThe Journal of biological chemistry2012
Critical determinants of human α-defensin 5 activity against non-enveloped viruses.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 72 citations in OpenAlex.
- Human alpha-defensin 5 stabilizes the enterovirus A71 capsid and blocks infection.bioRxiv : the preprint server for biology · 2026Article
- Vitamin D-Induced Antimicrobial Peptides in Combating Viral Infections.Advances in experimental medicine and biology · 2026Review
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Human Defensins: Structure, Function, and Potential as Therapeutic Antimicrobial Agents with Highlights Against SARS CoV-2.Probiotics and antimicrobial proteins · 2025Review
- Advances in the Role of Antimicrobial Peptides in the Management of Sexually Transmitted Infections.Journal of clinical laboratory analysis · 2025Review
- Advances in the Prevention of Cervical Cancer by Anti-Human Papillomavirus Agents.Cancer medicine · 2025Review
- Alpha-defensin binding expands human adenovirus tropism.PLoS pathogens · 2024Article
- A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins.Journal of virology · 2023Article
- Expanding the Landscape of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment in Nature, Implications for Peptide Design and Therapeutic Potential.International journal of molecular sciences · 2022Article
- Roles of Antimicrobial Peptides in Gynecological Cancers.International journal of molecular sciences · 2022Review
- The Inhibition of DNA Viruses by the Amphibian Antimicrobial Peptide Temporin G: A Virological Study Addressing HSV-1 and JPCyV.International journal of molecular sciences · 2022Article
- VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection.Journal of virology · 2022Article
- Are Host Defense Peptides and Their Derivatives Ready to be Part of the Treatment of the Next Coronavirus Pandemic?Archivum immunologiae et therapiae experimentalis · 2021Review
- Natural antimicrobial peptides as a source of new antiviral agents.The Journal of general virology · 2021Review
- Promising role of defensins peptides as therapeutics to combat against viral infection.Microbial pathogenesis · 2021Review
- Defensin-driven viral evolution.PLoS pathogens · 2020Article
- An Alphaherpesvirus Exploits Antimicrobial β-Defensins To Initiate Respiratory Tract Infection.Journal of virology · 2020Article
- Upregulated Expression of Intestinal Antimicrobial Peptide HD5 Associated with Renal Function in IgA Nephropathy.Disease markers · 2020Article
- Antiviral Activities of Human Host Defense Peptides.Current medicinal chemistry · 2020Review
- Defensins: A Double-Edged Sword in Host Immunity.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Human α-defensins, such as human α-defensin 5 (HD5), block infection of non-enveloped viruses, including human adenoviruses (AdV), papillomaviruses (HPV), and polyomaviruses. Through mutational analysis of HD5, we have identified arginine residues that contribute to antiviral activity against AdV and HPV. Of two arginine residues paired on one face of HD5, Arg-28 is critical for both viruses, while Arg-9 is only important for AdV. Two arginine residues on the opposite face of the molecule (Arg-13 and Arg-32) and unpaired Arg-25 are less important for both. In addition, hydrophobicity at residue 29 is a major determinant of anti-adenoviral activity, and a chemical modification that prevents HD5 self-association was strongly attenuating. Although HD5 binds to the capsid of AdV, the molecular basis for this interaction is undefined. Capsid binding by HD5 is not purely charge-dependent, as substitution of lysine for Arg-9 and Arg-28 was deleterious. Analysis of HD5 analogs that retained varying levels of potency demonstrated that anti-adenoviral activity is directly correlated with HD5 binding to the virus, confirming that the viral capsid rather than the cell is the relevant target. Also, AdV aggregation induced by HD5 binding is not sufficient for neutralization. Rather, these studies confirm that the major mechanism of HD5-mediated neutralization of AdV depends upon specific binding to the viral capsid through interactions mediated in part by critical arginine residues, hydrophobicity at residue 29, and multimerization of HD5, which increases initial binding of virus to the cell but prevents subsequent viral uncoating and genome delivery to the nucleus.
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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.