Characterization of Systemic Disease Development and Paw Inflammation in a Susceptible Mouse Model of Mayaro Virus Infection and Validation Using X-ray Synchrotron Microtomography

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de Carvalho, Ana Carolina ; Dias, Carlos Sato B. ; Coimbra, Lais D. ; Rocha, Rebeca P. F. ; Borin, Alexandre ; Fontoura, Marina A. ; Carvalho, Murilo ; Proost, Paul ; Nogueira, Mauricio L. ; Consonni, Silvio R. ; Sesti-Costa, Renata ; Marques, Rafael Elias

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 5, p. 17-pg., 2023-03-01.

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 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. (AU)

• FAPESP's process: 18/02594-9 - Development of a model of Usutu virus infection in mice: study of disease and testing of a neuroprotective compound
• Grantee: Rebeca de Paiva Froes Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/02993-0 - Development of the first experimental model of Ilheus Virus (ILHV) infection in mice and design of therapeutic strategies
• Grantee: Ana Carolina de Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/03917-6 - Mechanisms of disease susceptibility and resistance in experimental Mayaro fever in mice
• Grantee: Rafael Elias Marques Pereira Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/10990-1 - Characterization and therapeutic potential of chemokine action in sepsis and Flavivirus-induced encephalitis
• Grantee: Rafael Elias Marques Pereira Silva
• Support Opportunities: Regular Research Grants