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Modulating Chikungunya and Mayaro virus-induced disease severity in mice using low concentrations of anti-IFNAR1
Konrad Wesselmann1, Léa Luciani1,2, Gregory Moureau1
1Unité des Virus Émergents (UVE: Aix-Marseille Univ, Università di Corsica, IRD 190, Inserm 1207, IRBA), Marseille, France.
Abstract:
The laboratory mouse (Mus musculus) is the most widely used animal model for preclinical research, with numerous wild-type and genetically modified mouse strains available. Chikungunya virus (CHIKV), a mosquito-borne arthritogenic alphavirus, has emerged in various new regions and caused several millions of cases within the last decade. Mayaro virus (MAYV), an arthritogenic alphaviruses closely related to CHIKV, remains geographically restricted to the Americas. Existing mouse models rely on immunodeficient mice, leading to lethal illness, or footpad injection, which induces localized arthropathy. We present a proof-of-concept study demonstrating how disease severity in mice can be modulated using sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb). C57BL/6 mice were injected intraperitoneally with varying anti-IFNAR1 antibody doses before intraperitoneal infection with CHIKV or MAYV. For both, CHIKV and MAYV, we observed an anti-IFNAR1 mAb dose-dependent increase in blood viral loads and disease severity. A 1mg dose induced severe disease, whereas a 0.1 mg dose resulted in moderate symptoms in mice, mainly facial pain expression signs, accompanied by detectable viremia in the days preceding symptom onset. Viral loads in organs and serum concentrations of inflammatory cytokines and chemokines were also elevated in mice receiving 0.1mg anti-IFNAR1 mAb. In conclusion, we provide proof of concept that CHIKV and MAYV disease severity can be modulated using low concentrations of anti-IFNAR1 mAb. We used this approach to develop a new infection model for mild systemic disease, based on an accessible strain and a commercial antibody allowing for easy implementation and adaptation.
Insights
Researchers modulated Chikungunya virus (CHIKV) and Mayaro virus (MAYV) disease severity in mice using low doses of an interferon 1 receptor (IFNAR1) blocking antibody, creating a new model for mild systemic alphavirus infection.
Area of Science:
- Virology
- Immunology
- Preclinical Research
Background:
- Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are arthritogenic alphaviruses causing significant public health concerns.
- Current mouse models for CHIKV and MAYV often involve immunodeficient mice or localized infections, limiting their applicability.
- Developing adaptable and reproducible animal models is crucial for studying alphavirus pathogenesis and testing therapeutics.
Purpose of the Study:
- To demonstrate that disease severity in mice infected with CHIKV or MAYV can be modulated by sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb).
- To establish a novel, adaptable mouse model for studying mild systemic alphavirus infections.
Main Methods:
- C57BL/6 mice were administered varying doses of an anti-IFNAR1 mAb intraperitoneally.
- Mice were subsequently infected intraperitoneally with either CHIKV or MAYV.
- Viral loads, disease severity (including facial pain signs), viremia, and serum cytokine/chemokine levels were assessed.
Main Results:
- A dose-dependent increase in viral loads and disease severity was observed for both CHIKV and MAYV following anti-IFNAR1 mAb treatment.
- A 0.1 mg dose of anti-IFNAR1 mAb induced moderate disease with facial pain signs and detectable viremia.
- Elevated viral loads in organs and increased serum inflammatory markers were noted in mice treated with the lower mAb dose.
Conclusions:
- Sub-neutralizing concentrations of anti-IFNAR1 mAb effectively modulate CHIKV and MAYV disease severity in a dose-dependent manner.
- This approach successfully established a new mouse model for mild systemic alphavirus infection.
- The model utilizes accessible reagents and strains, facilitating easy implementation and adaptation for preclinical research.
