ArticleThe Journal of biological chemistry2012
Multifaceted mechanisms of HIV-1 entry inhibition by human α-defensin.
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 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- Vitamin D-Induced Antimicrobial Peptides in Combating Viral Infections.Advances in experimental medicine and biology · 2026Review
- Designing an optimized theta-defensin peptide for HIV therapy using in-silico approaches.Journal of integrative bioinformatics · 2025Article
- HNP-1: From Structure to Application Thanks to Multifaceted Functions.Microorganisms · 2025Review
- Understanding the Dynamics of Human Defensin Antimicrobial Peptides: Pathogen Resistance and Commensal Induction.Applied biochemistry and biotechnology · 2024Review
- Defensins: defenders of human reproductive health.Human reproduction update · 2023Review
- Review
- Antiviral Peptides (AVPs) of Marine Origin as Propitious Therapeutic Drug Candidates for the Treatment of Human Viruses.Molecules (Basel, Switzerland) · 2022Review
- Theta-Defensins to Counter COVID-19 as Furin Inhibitors:Computational and mathematical methods in medicine · 2022Article
- 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
- Article
- Peptide-Based Antiviral Drugs.Advances in experimental medicine and biology · 2021Article
- Antimicrobial host defence peptides: functions and clinical potential.Nature reviews. Drug discovery · 2020Review
- Fluorescence Microscopy of the HIV-1 Envelope.Viruses · 2020Review
- Defensins: A Double-Edged Sword in Host Immunity.Frontiers in immunology · 2020Review
- Antiviral Activities of Human Host Defense Peptides.Current medicinal chemistry · 2020Review
- HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.The Journal of biological chemistry · 2019Article
- Towards the Application of Human Defensins as Antivirals.Biomolecules & therapeutics · 2018Review
- Antivirals against animal viruses.Biochemical pharmacology · 2017Review
- Perspectives for clinical use of engineered human host defense antimicrobial peptides.FEMS microbiology reviews · 2017Review
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
The human neutrophil peptide 1 (HNP-1) is known to block the human immunodeficiency virus type 1 (HIV-1) infection, but the mechanism of inhibition is poorly understood. We examined the effect of HNP-1 on HIV-1 entry and fusion and found that, surprisingly, this α-defensin inhibited multiple steps of virus entry, including: (i) Env binding to CD4 and coreceptors; (ii) refolding of Env into the final 6-helix bundle structure; and (iii) productive HIV-1 uptake but not internalization of endocytic markers. Despite its lectin-like properties, HNP-1 could bind to Env, CD4, and other host proteins in a glycan- and serum-independent manner, whereas the fusion inhibitory activity was greatly attenuated in the presence of human or bovine serum. This demonstrates that binding of α-defensin to molecules involved in HIV-1 fusion is necessary but not sufficient for blocking the virus entry. We therefore propose that oligomeric forms of defensin, which may be disrupted by serum, contribute to the anti-HIV-1 activity perhaps through cross-linking virus and/or host glycoproteins. This notion is supported by the ability of HNP-1 to reduce the mobile fraction of CD4 and coreceptors in the plasma membrane and to precipitate a core subdomain of Env in solution. The ability of HNP-1 to block HIV-1 uptake without interfering with constitutive endocytosis suggests a novel mechanism for broad activity against this and other viruses that enter cells through endocytic pathways.
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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.