Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile

DENV-4 致死病例的肾脏损伤:病毒血症、免疫反应和细胞因子谱

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作者:Priscila Conrado Guerra Nunes, Lilimar da Silveira Rioja, Janice Mery Chicarino de Oliveira Coelho, Natália Gedeão Salomão, Kíssila Rabelo, Carollina Ceia José, Francisco das Chagas de Carvalho Rodrigues, Elzinandes Leal de Azeredo, Carlos Alberto Basílio-de-Oliveira, Rodrigo Basílio-de-Oliveira, Ri

Abstract

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.

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