ArticleProceedings of the National Academy of Sciences of the United States of America2015
Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanisms of XCR1 Membrane Trafficking and Constitutive Endocytosis.Basic & clinical pharmacology & toxicology · 2026Article
- Targeting of Kaposi's sarcoma-associated herpesvirus by immunotoxins directed against the viral G protein-coupled receptor, ORF74.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Exploring pUS27: Insights into Its Role in HCMV Pathogenesis and Potential for Antiviral Strategies.Pathogens (Basel, Switzerland) · 2025Review
- Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?Pathogens (Basel, Switzerland) · 2025Review
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis.Cellular & molecular biology letters · 2023Article
- Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges.Frontiers in immunology · 2023Review
- Viral G Protein-Coupled Receptors Encoded by β- and γ-Herpesviruses.Annual review of virology · 2022Review
- A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development.Cell reports methods · 2022Article
- The non-ELR CXC chemokine encoded by human cytomegalovirus UL146 genotype 5 contains a C-terminal β-hairpin and induces neutrophil migration as a selective CXCR2 agonist.PLoS pathogens · 2022Article
- Epstein-Barr Virus-Encoded BILF1 Orthologues From Porcine Lymphotropic Herpesviruses Display Common Molecular Functionality.Frontiers in endocrinology · 2022Article
- Review
- Review
- Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors.Molecules (Basel, Switzerland) · 2020Review
- Engineering Stem Cell Factor Ligands with Different c-Kit Agonistic Potencies.Molecules (Basel, Switzerland) · 2020Article
- Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential.Cancer immunology, immunotherapy : CII · 2020Article
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Advances in the treatment of cytomegalovirus.British medical bulletin · 2019Article
- The Golgi sorting motifs of human cytomegalovirus UL138 are not required for latency maintenance.Virus research · 2019Article
- HCMV latency: what regulates the regulators?Medical microbiology and immunology · 2019Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
The use of receptor-ligand interactions to direct toxins to kill diseased cells selectively has shown considerable promise for treatment of a number of cancers and, more recently, autoimmune disease. Here we move the fusion toxin protein (FTP) technology beyond cancer/autoimmune therapeutics to target the human viral pathogen, human cytomegalovirus (HCMV), on the basis of its expression of the 7TM G protein-coupled chemokine receptor US28. The virus origin of US28 provides an exceptional chemokine-binding profile with high selectivity and improved binding for the CX3C chemokine, CX3CL1. Moreover, US28 is constitutively internalizing by nature, providing highly effective FTP delivery. We designed a synthetic CX3CL1 variant engineered to have ultra-high affinity for US28 and greater specificity for US28 than the natural sole receptor for CX3CL1, CX3CR1, and we fused the synthetic variant with the cytotoxic domain of Pseudomonas Exotoxin A. This novel strategy of a rationally designed FTP provided unparalleled anti-HCMV efficacy and potency in vitro and in vivo.
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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.