ArticleJournal of virology2005
Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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
73 citing papers in PubMed, 160 citations in OpenAlex.
- Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures.Journal of virology · 2012Trial
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- Investigating the role of a conserved hydrophobic pocket of gp41 in the anti-HIV activity of fusion inhibitors.Protein science : a publication of the Protein Society · 2026Article
- Antiviral Drug Design: Past, Presence, and Future.Advances in experimental medicine and biology · 2026Review
- The conformational epitope of a gp41-specific mucosal protective IgA binds to the HIV-1 envelope and neutralizes infection.Acta pharmacologica Sinica · 2025Article
- The evolution of envelope function during coinfection with phylogenetically distinct human immunodeficiency virus.BMC infectious diseases · 2024Article
- Structure and Interactions of HIV-1 gp41 CHR-NHR Reverse Hairpin Constructs Reveal Molecular Determinants of Antiviral Activity.Journal of molecular biology · 2024Article
- Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV.Vaccines · 2023Article
- HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Opening the door on entry inhibitors in HIV: Redefining the use of entry inhibitors in heavily treatment experienced and treatment-limited individuals living with HIV.HIV medicine · 2022Review
- Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides.Biomedicines · 2021Review
- Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.Chemical reviews · 2021Review
- Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.Virulence · 2020Review
- A model of respiratory syncytial virus (RSV) infection of infants in newborn lambs.Cell and tissue research · 2020Review
- Assessment of Antibody Interference of Enfuvirtide (T20) Function Shows Assay Dependent Variability.Current HIV research · 2018Article
- Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors.The Journal of biological chemistry · 2017Article
- Review
- Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.Retrovirology · 2016Article
- Different infectivity of HIV-1 strains is linked to number of envelope trimers required for entry.PLoS pathogens · 2015Article
- Resistance to N-peptide fusion inhibitors correlates with thermodynamic stability of the gp41 six-helix bundle but not HIV entry kinetics.Retrovirology · 2014Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Enfuvirtide (ENF/T-20/Fuzeon), the first human immunodeficiency virus (HIV) entry inhibitor to be licensed, targets a structural intermediate of the entry process. ENF binds the HR1 domain in gp41 after Env has bound CD4, preventing conformational changes needed for membrane fusion. Mutations in HR1 that confer ENF resistance can arise following ENF therapy. ENF resistance mutations were introduced into an R5- and X4-tropic Env to examine their impact on fusion, infection, and sensitivity to different classes of entry inhibitors and neutralizing antibodies. HR1 mutations could reduce infection and fusion efficiency and also delay fusion kinetics, likely accounting for their negative impact on viral fitness. HR1 mutations had minimal effect on virus sensitivity to other classes of entry inhibitors, including those targeting CD4 binding (BMS-806 and a CD4-specific monoclonal antibody [MAb]), coreceptor binding (CXCR4 inhibitor AMD3100 and CCR5 inhibitor TAK-779), or fusion (T-1249), indicating that ENF-resistant viruses can remain sensitive to other entry inhibitors in vivo. Some HR1 mutations conferred increased sensitivity to a subset of neutralizing MAbs that likely target fusion intermediates or with epitopes preferentially exposed following receptor interactions (17b, 48D, 2F5, 4E10, and IgGb12), as well as sera from some HIV-positive individuals. Mechanistically, enhanced neutralization correlated with reduced fusion kinetics, indicating that, in addition to steric constraints, kinetics may also limit virus neutralization by some antibodies. Therefore, escape from ENF comes at a cost to viral fitness and may confer enhanced sensitivity to humoral immunity due to prolonged exposure of epitopes that are not readily accessible in the native Env trimer. Resistance to other entry inhibitors was not observed.
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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.