Pathogenicity of Lloviu and Bombali Viruses in Type I Interferon Receptor Knockout Mice

Author:

Fletcher Paige1,Feldmann Friederike2,Takada Ayato3,Crossland Nicholas A45,Hume Adam J46,Albariño César7,Kemenesi Gábor89,Feldmann Heinz1ORCID,Mühlberger Elke46,Marzi Andrea1ORCID

Affiliation:

1. Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, Montana , USA

2. Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, Montana , USA

3. Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University , Sapporo , Japan

4. National Emerging Infectious Diseases Laboratories, Boston University School of Medicine , Boston, Massachusetts , USA

5. Department of Pathology and Laboratory Medicine, Boston University School of Medicine , Boston, Massachusetts , USA

6. Department of Microbiology, Boston University School of Medicine , Boston, Massachusetts , USA

7. Viral Special Pathogens Branch, Centers for Disease Control and Prevention , Atlanta, Georgia , USA

8. National Laboratory of Virology, Szentágothai Research Center, University of Pécs , Pécs , Hungary

9. Institute of Biology, Faculty of Sciences, University of Pécs , Pécs , Hungary

Abstract

Abstract 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 infected IFNAR−/− mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (IN) or intraperitoneal (IP) route and compared virus loads at early and late time points after infection. No signs of disease and no viral RNA were detected after IN infection regardless of LLOV dose. In contrast, IP infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early time point. The low-dose LLOV and BOMV groups achieved higher viral loads at the late time point. 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.

Funder

Division of Intramural Research

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Japan Agency for Medical Research and Development

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference35 articles.

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