Pathogenicity of Lloviu and Bombali viruses in IFNAR-/- mice.

Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response, therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We sought to assess the pathogenicity of emerging wildtype filovirus infections in IFNAR-/- mice since filovirus models using immunocompetent mice require a mouse-adapted viral strain. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (i.n.) or intraperitoneal (i.p.) route and compared virus loads at early and late timepoints after infection. No signs of disease and no viral RNA were detected after i.n. infection regardless of LLOV dose. In contrast, i.p. infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early timepoint. The low-dose LLOV and BOMV groups achieved higher viral loads at the late timepoint. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.