Natália Gedeão Salomão ^1,2* Luciana Araújo ³ Luiz De Souza ⁴ Anna Luiza ⁴ Carlos Basílio-De- Oliveira ³ Rodrigo Panno Basilio-de-Oliveira ³ Jorge José Carvalho ⁵ Priscila Nunes ⁶ Juliana Da Silva ⁷ Douglas Barbosa ⁷ Marciano Paes ⁸ Kíssila Rabelo ⁹ FLAVIA Barreto Dos Santos ⁶

• ¹ Laboratório das Interações Vírus-Hospedeiros, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
• ² Laboratório Interdisciplinar de Pesquisas Médicas, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Paraná, Brazil
• ³ Departamento de Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Paraná, Brazil
• ⁴ Faculdade de Medicina de Campos, Campos dos Goytacazes, Rio de Janeiro, Brazil
• ⁵ Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Paraná, Brazil
• ⁶ Laboratório das Interações Vírus-Hospedeiros, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Paraná, Brazil
• ⁷ Laboratório de Análise Imunomolecular, Institute of Technology in Immunobiology, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil
• ⁸ Laboratório Interdisciplinar de Pesquisas Médicas, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brazil
• ⁹ Laboratório de Ultraestrutura e Biologia Tecidual, Rio de Janeiro State University, Rio de Janeiro, Rio de Janeiro, Brazil

Alphavirus chikungunya virus (CHIKV) is an arbovirus, belonging to the Togaviridae family. The disease caused by CHIKV generally evolves with spontaneous resolution in a few weeks, however, the progression to a chronic disease may occur. The most common symptoms are fever, myalgia and arthralgia; however, skin manifestations may occur in 40 to 80% of infected individuals. Morbilliform and maculopapular erythematous eruptions, vesiculobullous lesions, generalized erythema, maculopapular eruption and skin peeling, hypermelanosis, painful oral lesions and urticarial lesions have been reported. Usually these manifestations disappear, but they can become sequelae. Since the skin is the first line of defense against CHIKV infection, here we aimed to investigate the immunohistopathological aspects of the skin of infected individuals during the acute phase of the disease by performing histopathological and ultrastructural analysis, detection and quantification of viral genome, detection of viral antigen and immune cells and cytokines/chemokines' characterization. The main histopathological findings were perivascular and inflammatory infiltrates, blood capillary ectasia and interstitial edema. The immunohistochemistry revealed CHIKV antigen in the epidermis, endothelial cells, fibroblast and macrophages in the reticular and papillary dermis, inflammatory cells infiltrate, arrector pili muscle, sweat and sebaceous glands, in addition to the hair follicle. Moreover, inflammatory infiltrates were composed by lymphocytes (CD4 + and CD8 + ) and macrophages (CD68 + ) in the dermis and in perivascular infiltrate. TNF-α, IL-6, RANTES and VEGFR2 were expressed in the epidermis, blood vessels, sweat glands and in migrating cells. Loss of contact among adjacent keratinocytes, epidermis presenting necrotic cells and fibroblasts with dilated cisternae in endoplasmic reticulum and mitochondria with few cristae were observed by transmission electron microscopy. Studies involving skin immunopathogenesis during CHIKV infection are still scarce, therefore the findings presented here can contribute to a better understanding of the disease immunopathogenesis.