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<p>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.</p>

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Sulfated glycosaminoglycans inhibit LCMV entry and modulate antiviral immunity and pathology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Michal Gorzkiewicz,
  • Soha Noseir,
  • Mandar Vengurlekar,
  • Mitrajit Ghosh,
  • Ichiro Katahira,
  • Džiuljeta Abromavičiūtė,
  • Ulla Gerling-Driessen,
  • Lorand Bonda,
  • Nick Rähse,
  • Marco Lapsien,
  • Sabrina Bockholt,
  • Ann Kathrin Bergmann,
  • Konstantina Kostadinovska,
  • Hafssa Fraii,
  • Karl S Lang,
  • Lisa Oestereich,
  • Holger Gohlke,
  • Laura Hartmann,
  • Philipp A Lang

摘要

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.