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

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 5, p. 17-pg., 2023-03-01.

Resumo

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)

• Processo FAPESP: 18/02594-9 - Estabelecimento de um modelo de infecção por usutu virus em camundongos: estudo da doença e teste de um composto neuroprotetor
• Beneficiário: Rebeca de Paiva Froes Rocha
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/02993-0 - Desenvolvimento do primeiro modelo experimental de infecção por Vírus Ilhéus (ILHV) em camundongos e delineamento de estratégias terapêuticas
• Beneficiário: Ana Carolina de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/03917-6 - Mecanismos de doença e resistência envolvidos na febre do Mayaro em camundongos
• Beneficiário: Rafael Elias Marques Pereira Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/10990-1 - Caracterização e potencial terapêutico de quimiocinas em sepse e encefalite induzida por Flavivirus
• Beneficiário: Rafael Elias Marques Pereira Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular