Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/ijms24054799
Keywords
mayaro virus; alphavirus; innate immunity; inflammation; microtomography; synchrotron technology
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Mayaro virus is an emerging arthropod-borne virus endemic in Latin America, causing arthritogenic febrile disease. In this study, a mouse model lacking type-I interferon receptor was used to explore the disease progression. The results showed that Mayaro virus infection in the hind paws of these mice led to visible inflammation, disseminated infection, and immune response activation. The histological analysis revealed edema in multiple tissues, which was associated with viral replication and the recruitment of immune cells.
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 mu m(3). 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.
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