A Surrogate BSL2-compliant Infection Model Recapitulating Key Aspects of Human Marburg Virus Disease

Marburg virus disease (MVD) is a severe infectious disease characterized by fever and profound hemorrhage caused by the Marburg virus (MARV), with a mortality rate reaching 90%, posing a significant threat to humans. MARV lies in its classification as a biosafety level four (BSL-4) pathogen, which demands stringent experimental conditions and substantial funding. 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) and utilized it as a surrogate to induce lethal infection in hamsters. Syrian hamsters infected with VSV-MARV/GP presented symptoms such as thrombocytopenia, lymphopenia, hemophilia, and multiorgan failure, developing a severe systemic disease akin to that observed in human MARV patients, with all animals succumbing to infection at 2 to 3 days post-infection (dpi). Notably, the pathogenicity of VSV-MARV/GP 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.