Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile
by
Priscila Conrado Guerra Nunes 1,*
, Lilimar da Silveira Rioja 2, Janice Mery Chicarino de Oliveira Coelho 3, Natália Gedeão Salomão 4, Kíssila Rabelo 5, Carollina Ceia José 4, Francisco das Chagas de Carvalho Rodrigues 3, Elzinandes Leal de Azeredo 1, Carlos Alberto Basílio-de-Oliveira 6, Rodrigo Basílio-de-Oliveira 6, Rita Maria Ribeiro Nogueira 7, Juan Camilo Sánchez-Arcila 8, Flávia Barreto dos Santos 1,† and Marciano Viana Paes 4,*,†
Priscila Conrado Guerra Nunes 1,*, Lilimar da Silveira Rioja 2, Janice Mery Chicarino de Oliveira Coelho 3, Natália Gedeão Salomão 4, Kíssila Rabelo 5, Carollina Ceia José 4, Francisco das Chagas de Carvalho Rodrigues 3, Elzinandes Leal de Azeredo 1, Carlos Alberto Basílio-de-Oliveira 6, Rodrigo Basílio-de-Oliveira 6, Rita Maria Ribeiro Nogueira 7, Juan Camilo Sánchez-Arcila 8, Flávia Barreto dos Santos 1,† and Marciano Viana Paes 4,*,†
1
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro-RJ 21040900, Brazil
2
Departamento de Patologia e Laboratórios, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro-RJ 20550170, Brazil
3
Laboratório de Anatomia Patológica, Instituto Nacional de Infectologia, Fundação Oswaldo Cruz /FIOCRUZ, Rio de Janeiro-RJ 21040900, Brazil
4
Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz /FIOCRUZ, Rio de Janeiro-RJ 21040900, Brazil
5
Laboratório de Ultraestrutura e Biologia Tecidual, Universidade do Estado do Rio de Janeiro/UERJ, Rio de Janeiro- RJ 20550170, Brazil
6
Anatomia Patológica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro-RJ 20270004, Brazil
7
Laboratório de Flavivirus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz /FIOCRUZ Rio de Janeiro-RJ 21040900, Brazil
8
School of Natural Sciences, University of California, Merced-CA 95343, USA
*
Authors to whom correspondence should be addressed.
†
Those authors contributed equally to the work.
Pathogens 2019, 8(4), 223; https://doi.org/10.3390/pathogens8040223
Received: 9 September 2019 / Revised: 14 October 2019 / Accepted: 19 October 2019 / Published: 7 November 2019
(This article belongs to the Section Human Pathogens)
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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Keywords:
dengue 4; fatal case; viremia; histopathology; cytokines; inflammatory mediators
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MDPI and ACS Style
Nunes, P.C.G.; Rioja, L.S.; Coelho, J.M.C.O.; Salomão, N.G.; Rabelo, K.; José, C.C.; Rodrigues, F.C.C.; de Azeredo, E.L.; Basílio-de-Oliveira, C.A.; Basílio-de-Oliveira, R.; Nogueira, R.M.R.; Sánchez-Arcila, J.C.; dos Santos, F.B.; Paes, M.V. Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile. Pathogens 2019, 8, 223.
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