Characterization of Systemic Disease Development and Paw Inflammation in a Susceptible Mouse Model of Mayaro Virus
Ana Carolina de Carvalho1,2,3, Carlos Sato B Dias4, Laís D Coimbra1,2
1Brazilian National Biosciences Laboratory-LNBio, Brazilian Center for Research in Energy and Materials-CNPEM, R. Giuseppe Máximo Scolfaro, 10000-Bosque das Palmeiras, Campinas 13083-100, Brazil.
Abstract:
Mayaro virus (MAYV) is an emerging arthropod-borne virus endemic in Latin America and the causative agent of arthritogenic febrile disease. Mayaro fever is poorly understood; thus, we established an in vivo model of infection in susceptible type-I interferon receptor-deficient mice (IFNAR-/-) to characterize the disease. MAYV inoculations in the hind paws of IFNAR-/- mice result in visible paw inflammation, evolve into a disseminated infection and involve the activation of immune responses and inflammation. The histological analysis of inflamed paws indicated edema at the dermis and between muscle fibers and ligaments. Paw edema affected multiple tissues and was associated with MAYV replication, the local production of CXCL1 and the recruitment of granulocytes and mononuclear leukocytes to muscle. We developed a semi-automated X-ray microtomography method to visualize both soft tissue and bone, allowing for the quantification of MAYV-induced paw edema in 3D with a voxel size of 69 µm3. The results confirmed early edema onset and spreading through multiple tissues in inoculated paws. In conclusion, we detailed features of MAYV-induced systemic disease and the manifestation of paw edema in a mouse model extensively used to study infection with alphaviruses. The participation of lymphocytes and neutrophils and expression of CXCL1 are key features in both systemic and local manifestations of MAYV disease.
Insights
Mayaro virus (MAYV) causes arthritogenic febrile disease. This study developed a mouse model to characterize MAYV infection, revealing paw edema and systemic inflammation involving immune cell recruitment and CXCL1 expression.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Mayaro virus (MAYV) is an emerging arthropod-borne virus causing arthritogenic febrile disease in Latin America.
- The pathogenesis of Mayaro fever remains poorly understood, necessitating further investigation.
Purpose of the Study:
- To establish and characterize an in vivo mouse model for Mayaro virus infection.
- To investigate the immune responses and inflammatory processes associated with MAYV disease.
Main Methods:
- Utilized type-I interferon receptor-deficient (IFNAR-/-) mice for MAYV inoculation in hind paws.
- Employed histological analysis and semi-automated X-ray microtomography for quantifying paw edema and tissue changes.
- Assessed immune cell infiltration (granulocytes, mononuclear leukocytes, lymphocytes, neutrophils) and CXCL1 expression.
Main Results:
- MAYV infection in IFNAR-/- mice induced visible paw inflammation, edema, and disseminated disease.
- Histological analysis revealed edema in dermis, muscle fibers, and ligaments, associated with viral replication.
- X-ray microtomography quantified early onset and spreading of paw edema.
- Confirmed recruitment of granulocytes, mononuclear leukocytes, lymphocytes, and neutrophils, alongside CXCL1 production.
Conclusions:
- Established a relevant mouse model for studying Mayaro virus disease.
- Detailed systemic disease features and paw edema manifestation in MAYV infection.
- Highlighted the role of lymphocytes, neutrophils, and CXCL1 in MAYV pathogenesis.
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