Sulfated glycosaminoglycans inhibit LCMV entry and modulate antiviral immunity and pathology
Viral infections remain a major challenge due to the limited availability and efficacy of current treatments. Existing antivirals primarily target viral replication but are often virus-specific and can lead to drug resistance. Sulfated glycosaminoglycans (GAGs) have emerged as promising broad-spectrum agents that block viral binding and entry into host cells. Here, we show that highly sulfated GAGs restrict the infectivity of both pathogenic and non-pathogenic Arenaviruses. Using the lymphocytic choriomeningitis virus (LCMV) model, we demonstrate that GAG exposure reduces viral entry and infection in cell lines and bone marrow-derived dendritic cells, impairing their ability to activate antiviral T cells. In vivo, early exposure of LCMV to dextran sulfate suppressed immune activation, leading to diminished T-cell responses, prolonged infection, and increased immunopathology. By contrast, administering dextran sulfate during the acute infection phase decreased viral load, improved effector T-cell function, and reduced liver pathology. These findings highlight the therapeutic potential of sulfated GAGs against Arenavirus infections and the importance of treatment timing for clinical efficacy.
Authors
- Philipp A. Lang (ORCID: https://orcid.org/0000-0001-5341-0407)
- Mitrajit Ghosh (ORCID: https://orcid.org/0000-0002-2969-219X)
- Lisa Oestereich (ORCID: https://orcid.org/0000-0003-0098-7485)
- Ann Kathrin Bergmann (ORCID: https://orcid.org/0000-0002-0828-4154)
- Lorand Bonda
- Karl S. Lang (ORCID: https://orcid.org/0000-0001-9783-7605)
- Soha Noseir
- Ulla Gerling-Driessen
- Sabrina Bockholt
- Ichiro Katahira (ORCID: https://orcid.org/0009-0004-9353-1886)
- Džiuljeta Abromavičiūtė (ORCID: https://orcid.org/0009-0001-4451-7031)
- Marco Lapsien
- Nick Rähse
- Mandar Vengurlekar
- Michal Gorzkiewicz
- Laura Hartmann
- Holger Gohlke
- Hafssa Fraii
- Konstantina Kostadinovska
Institutions
- University of Freiburg (DE)
- Forschungszentrum Jülich (DE)
- University of Łódź (PL)
- Düsseldorf University Hospital (DE)
- German Center for Infection Research (DE)
- Essen University Hospital (DE)
- Heinrich Heine University Düsseldorf (DE)
- Bernhard Nocht Institute for Tropical Medicine (DE)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2026-02-23
- DOI
- https://doi.org/10.1038/s44321-026-00387-8
- Primary Topic
- Viral Infections and Outbreaks Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Jürgen Manchot Stiftung
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Bundesministerium für Bildung und Forschung
- Heinrich-Heine-Universität Düsseldorf
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases