Marburg Virus Glycoprotein Is a Remarkable Virulent Factor Linked to Hemorrhagic Pathology: Evidence from Multimodal...

Marburg virus (MARV) causes Marburg virus disease (MVD), a severe hemorrhagic fever associated with high morbidity and mortality. No specific antiviral therapies are currently approved for MVD, and viral pathogenesis, particularly the viral pathogenic factor(s) involved, remains poorly defined. Here, we demonstrated that MARV glycoprotein (GP) can induce rounding and detachment of adherent cells, likely by shielding and downregulating cell surface molecules, mainly via its mucin-like domain (MLD), disrupting monolayer barrier function. In an ex vivo rat vascular model, GP expression caused significant endothelial cell damage and increased vascular permeability. In vivo, MARV GP increases vascular permeability and exacerbates inflammation and tissue injury in mouse muscle and liver transduction models, validating its pathogenic activity. Deletion of the MLD largely abolished these pathogenic effects, indicating its significant role in MARV GP pathogenicity. In addition, using the ex vivo vascular model, we demonstrated the infectivity and pathogenicity of the authentic Ebola virus in vessels and validated the utility of this model as a tool for intervention research against filovirus infection and GP pathogenicity. This study uncovered the remarkable role of MARV GP as a hemorrhage-related pathogenic factor through multimodal analyses, which may help advance our understanding of viral pathogenesis and lay a foundation for future therapeutic strategies.