A surrogate BSL2-compliant infection model recapitulating key aspects of human Marburg virus disease

Emerg Microbes Infect. 2025 Dec;14(1):2449083. doi: 10.1080/22221751.2024.2449083. Epub 2025 Jan 12.

Abstract

Marburg virus disease (MVD) is a severe infectious disease caused by the Marburg virus (MARV), posing a significant threat to humans. MARV needs to be operated under strict biosafety Level 4 (BSL-4) laboratory conditions. Therefore, accessible and practical animal models are urgently needed to advance prophylactic and therapeutic strategies for MARV. In this study, we constructed a recombinant vesicular stomatitis virus (VSV) expressing the Marburg virus glycoprotein (VSV-MARV/GP). Syrian hamsters infected with VSV-MARV/GP presented symptoms such as thrombocytopenia, lymphopenia, haemophilia, and multiorgan failure, developing a severe systemic disease akin to that observed in human MARV patients. Notably, the pathogenicity was found to be species-specific, age-related, sex-associated, and challenge route-dependent. Subsequently, the therapeutic efficacy of the MR191 monoclonal antibody was validated in this model. In summary, this alternative model is an effective tool for rapidly screening medical countermeasures against MARV GP in vivo under BSL-2 conditions.

Keywords: Marburg virus; Syrian hamster; recombinant vesicular stomatitis virus; recurrence of classic symptoms; surrogate model; vaccine evaluation and drug screening.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / immunology
  • Containment of Biohazards
  • Cricetinae
  • Disease Models, Animal*
  • Female
  • Glycoproteins / genetics
  • Humans
  • Male
  • Marburg Virus Disease* / virology
  • Marburgvirus* / genetics
  • Marburgvirus* / pathogenicity
  • Mesocricetus*
  • Vesiculovirus / genetics
  • Vesiculovirus / pathogenicity
  • Vesiculovirus / physiology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism

Substances

  • Antibodies, Viral
  • Antibodies, Monoclonal
  • Glycoproteins
  • Viral Envelope Proteins

Grants and funding

This work was supported by the National Key R&D Program of China (grant number: 2023YFC2605500).