Dataset Information

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

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 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.

SUBMITTER: Fletcher P

PROVIDER: S-EPMC10651197 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Fletcher Paige P Feldmann Friederike F Takada Ayato A Crossland Nicholas A NA Hume Adam J AJ Albariño César C Kemenesi Gábor G Feldmann Heinz H Mühlberger Elke E Marzi Andrea A

The Journal of infectious diseases 20231101 Suppl 7

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 rega ...[more]

PMID: 37352146

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Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently a global pandemic with unprecedented public health, economic and social impact. The development of effective mitigation strategies, therapeutics and vaccines relies on detailed genomic and biological characterization of the regional viruses. This study was carried out to isolate SARS-CoV-2 viruses circulating in Anatolia, and to investigate virus propagation in frequently-used cells and experimental animals. We obtained two SARS-CoV-2 viruses from nasopharngeal swabs of confirmed cases in Vero E6 cells, visualized the virions using atomic force and scanning electron microscopy and determined size distribution of the particles. Viral cytopathic effects on Vero E6 cells were initially observed at 72 h post-inoculation and reached 90% of the cells on the 5th day. The isolates displayed with similar infectivity titers, time course and infectious progeny yields. Genome sequencing revealed the viruses to be well-conserved, with less than 1% diversity compared to the prototype virus. The analysis of the viral genomes, along with the available 62 complete genomes from Anatolia, showed limited diversity (up to 0.2% on deduced amino acids) and no evidence of recombination. The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%. The isolates produced non-fatal infection in the transgenic type I interferon knockout (IFNAR-/-) mice, with varying neutralizing antibody titers. Hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy, with similar histopathological and immunohistochemistry findings in the lungs, heart, stomach, intestines, liver, spleen and kidneys. Peak viral loads were detected in the lungs, with virus RNA present in the kidneys, jejunum, liver, spleen and heart. In conclusion, we characterized two local isolates, investigated in vitro growth dynamics in Vero E6 cells and identified IFNAR-/- mice as a potential animal model for SARS-CoV-2 experiments.

Dataset Information

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

Publications

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

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