Mouse models of Ebola virus tolerance and lethality: characterization of CD-1 mice infected with wild-type, guinea pig-adapted, or mouse-adapted virus

• Published in: Antiviral research 2023-02, Vol.210 (C), p.105496-105496, Article 105496
• Main Authors: Spengler, Jessica R., Welch, Stephen R., Ritter, Jana M., Harmon, Jessica R., Coleman-McCray, JoAnn D., Genzer, Sarah C., Seixas, Josilene N., Scholte, Florine E.M., Davies, Katherine A., Bradfute, Steven B., Montgomery, Joel M., Spiropoulou, Christina F.
• Format: Article
• Language: English
• Subjects: Animals; CD-1 mice; Clinical pathology; Convalescence; Disease Models, Animal; Ebola virus; Ebolavirus - genetics; Guinea Pigs; Hemorrhagic Fever, Ebola; Histopathology; Humans; Mice; Mouse models; Survivor
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2022.105496

Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV resulted in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant did not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice. These data support future investigations of pathogenesis, convalescence, and sequelae in mouse models of virus tolerance. •Like wild-type Ebola virus, guinea pig-adapted Ebola virus causes mild infection in CD-1 mice.•Ebola virus disseminates and replicates widely in mice infected with lethal and non-lethal variants.•Viral tolerance is correlated with early type I IFN responses and reduced inflammation.•Non-lethal Ebola virus infection causes transient liver pathology and sustained lymphoid reactivity.