Species-specific gene programs define divergent antiviral responses in Marburg virus reservoir bats and humans
Bats tolerate viruses that cause severe disease in humans. Egyptian rousette bats, the natural reservoirs of Marburg virus (MARV), sustain asymptomatic infection, whereas humans develop severe and fatal disease. To define the basis of this divergence, we establish a comparative framework using primary and immortalized Egyptian rousette and human cells exposed to double-stranded RNA and interferon (IFN). Bat cells upregulate antiviral effectors while limiting inflammatory amplifiers, a pattern further supported by analysis of independent in vivo MARV infection datasets. In contrast, human cells activate antiviral programs and immune hyperactivation in response to MARV. Integrating transcriptomic and proteomic analyses, we identify species-specific immune programs encompassing differential IFN-stimulated gene regulation, apoptotic control, and cytokine signaling. Our findings establish an integrative framework for understanding species-specific antiviral responses associated with MARV reservoir biology, identify pathways linked to immunopathogenesis in humans, and provide a foundation for future studies of host responses to filovirus infection.
Authors
- Adolfo Garcı́a-Sastre (ORCID: https://orcid.org/0000-0002-6551-1827)
- Jens H. Kuhn (ORCID: https://orcid.org/0000-0002-7800-6045)
- Jeffrey R. Johnson (ORCID: https://orcid.org/0000-0002-4221-298X)
- N.M. Ferressini Gerpe (ORCID: https://orcid.org/0000-0003-1210-3085)
- André Filipe Pastor (ORCID: https://orcid.org/0000-0002-5133-9616)
- Mariano Sánchez-Lockhart (ORCID: https://orcid.org/0000-0001-8009-7540)
- Maya Tagliavia (ORCID: https://orcid.org/0009-0007-4415-8116)
- Jonathan S. Towner (ORCID: https://orcid.org/0000-0002-6473-3049)
- Juan Ángel Patin͂o-Galindo (ORCID: https://orcid.org/0000-0002-6832-7179)
- Jonathan C. Guito (ORCID: https://orcid.org/0000-0002-1063-7473)
- Elaina Giannetti
- Gabriella Worwa (ORCID: https://orcid.org/0000-0001-7485-2204)
- Gustavo F. Palacios (ORCID: https://orcid.org/0000-0001-5062-1938)
- Shruti Shirsathe (ORCID: https://orcid.org/0000-0001-7556-233X)
- Heng Pan
- Rachel Somavarapu (ORCID: https://orcid.org/0000-0001-6016-4021)
- Santiago Vidal-Freire
Institutions
- Centers for Disease Control and Prevention (US)
- National Institutes of Health (US)
- University of Georgia (US)
- United States Army Medical Research Institute of Infectious Diseases (US)
- National Center for Emerging and Zoonotic Infectious Diseases (US)
- National Institute of Allergy and Infectious Diseases (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-10-27
- DOI
- https://doi.org/10.1016/j.celrep.2026.118217
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases