Lethal Sudan virus infection in IFNAR-/- mice is characterized by key inflammatory features of filovirus disease.

Sudan virus (SUDV) is a member of the family Filoviridae, which comprises highly pathogenic viruses associated with unusually high case fatality rates. The development of medical countermeasures against filoviruses, including antivirals, vaccines, and therapeutic antibodies, requires preclinical evaluation in suitable animal models. C57BL/6J IFNAR-/- mice, which lack the type I interferon (IFN-α/β) receptor, have been reported to be susceptible to filovirus infections, although their impaired innate immune response may represent a potential limitation of the model. Here, we characterized the clinical, virological, pathological, and inflammatory responses following SUDV Boniface infection in IFNAR-/- mice. Following infection, animals developed progressive clinical disease characterized by substantial weight loss and pronounced changes in behavior and appearance. Mice reached the predefined clinical endpoint 3-5 days post infection. Post mortem analysis of terminal samples revealed high viral loads and viral genome copies in all tested organs as well as in serum, consistent with widespread systemic dissemination. Histopathological examination revealed prominent lesions, particularly in the liver and spleen. In addition, terminal serum analysis revealed a broad and pronounced inflammatory response, with significantly elevated concentrations of multiple cytokines and chemokines compared with non-infected controls, encompassing pro-inflammatory, regulatory, and hematopoietic mediators. Together, these findings characterize the clinical course, systemic viral dissemination, tissue pathology, and terminal inflammatory response associated with lethal SUDV infection in IFNAR-/- mice. The observed cytokine and chemokine elevations are consistent with inflammatory responses described in filovirus infections, although the single terminal sampling time point and limited cohort size preclude conclusions regarding the temporal development or mechanistic basis of this response. These data support the utility of this model for investigating filovirus pathogenesis and infection-associated immune responses and warrant further evaluation of its suitability for SUDV infection and for preclinical studies of filovirus countermeasures.