Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype

Dengue virus type 2 (DENV-2) is, traditionally, the most studied serotype due to its association with explosive outbreaks and severe cases. In Brazil, almost 20 years after the first introduction in the 1990s, a new lineage (Lineage II) of the DENV-2 Asian/American genotype emerged and caused an epi...

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Main Authors: Fernanda Cunha Jácome, Gabriela Cardoso Caldas, Arthur da Costa Rasinhas, Ana Luisa Teixeira de Almeida, Daniel Dias Coutinho de Souza, Amanda Carlos Paulino, Marcos Alexandre Nunes da Silva, Ortrud Monika Barth, Flávia Barreto dos Santos, Debora Ferreira Barreto-Vieira
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/10/9/1084
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author Fernanda Cunha Jácome
Gabriela Cardoso Caldas
Arthur da Costa Rasinhas
Ana Luisa Teixeira de Almeida
Daniel Dias Coutinho de Souza
Amanda Carlos Paulino
Marcos Alexandre Nunes da Silva
Ortrud Monika Barth
Flávia Barreto dos Santos
Debora Ferreira Barreto-Vieira
author_facet Fernanda Cunha Jácome
Gabriela Cardoso Caldas
Arthur da Costa Rasinhas
Ana Luisa Teixeira de Almeida
Daniel Dias Coutinho de Souza
Amanda Carlos Paulino
Marcos Alexandre Nunes da Silva
Ortrud Monika Barth
Flávia Barreto dos Santos
Debora Ferreira Barreto-Vieira
author_sort Fernanda Cunha Jácome
collection DOAJ
description Dengue virus type 2 (DENV-2) is, traditionally, the most studied serotype due to its association with explosive outbreaks and severe cases. In Brazil, almost 20 years after the first introduction in the 1990s, a new lineage (Lineage II) of the DENV-2 Asian/American genotype emerged and caused an epidemic with severe cases and hospitalizations. Severe dengue includes multiple organ failure, and renal involvement can be potentially related to increased mortality. In order to better understand the role of DENV infection in renal injury, here we aimed to investigate the outcomes of infection with two distinct lineages of DENV-2 Asian/American genotype in the kidney of a murine model. BALB/c mice were infected with Lineages I and II and tissues were submitted to histopathology, immunohistochemistry, histomorphometry and ultrastructural analysis. Blood urea nitrogen (BUN) was detected in blood sample accessed by cardiac puncture. A tendency in kidney weight increase was observed in mice infected with both lineages, but urea levels, on average, were increased only in mice infected with Lineage II. The DENV antigen was detected in the tissue of mice infected with Lineage II and morphological changes were similar to those observed in human dengue cases. Furthermore, the parameters such as organ weight, urea levels and morphometric analysis, showed significant differences between the two lineages in the infected BALB/c, which was demonstrated to be a suitable experimental model for dengue pathophysiology studies in kidneys.
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spelling doaj.art-f328ef21ca844237828b414af67af6622023-11-22T14:41:28ZengMDPI AGPathogens2076-08172021-08-01109108410.3390/pathogens10091084Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American GenotypeFernanda Cunha Jácome0Gabriela Cardoso Caldas1Arthur da Costa Rasinhas2Ana Luisa Teixeira de Almeida3Daniel Dias Coutinho de Souza4Amanda Carlos Paulino5Marcos Alexandre Nunes da Silva6Ortrud Monika Barth7Flávia Barreto dos Santos8Debora Ferreira Barreto-Vieira9Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Immunology, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 2104-90, RJ, BrazilDengue virus type 2 (DENV-2) is, traditionally, the most studied serotype due to its association with explosive outbreaks and severe cases. In Brazil, almost 20 years after the first introduction in the 1990s, a new lineage (Lineage II) of the DENV-2 Asian/American genotype emerged and caused an epidemic with severe cases and hospitalizations. Severe dengue includes multiple organ failure, and renal involvement can be potentially related to increased mortality. In order to better understand the role of DENV infection in renal injury, here we aimed to investigate the outcomes of infection with two distinct lineages of DENV-2 Asian/American genotype in the kidney of a murine model. BALB/c mice were infected with Lineages I and II and tissues were submitted to histopathology, immunohistochemistry, histomorphometry and ultrastructural analysis. Blood urea nitrogen (BUN) was detected in blood sample accessed by cardiac puncture. A tendency in kidney weight increase was observed in mice infected with both lineages, but urea levels, on average, were increased only in mice infected with Lineage II. The DENV antigen was detected in the tissue of mice infected with Lineage II and morphological changes were similar to those observed in human dengue cases. Furthermore, the parameters such as organ weight, urea levels and morphometric analysis, showed significant differences between the two lineages in the infected BALB/c, which was demonstrated to be a suitable experimental model for dengue pathophysiology studies in kidneys.https://www.mdpi.com/2076-0817/10/9/1084dengue 2Asian/American lineagesBALB/c micekidneyhistopathology and transmission electron microscopy
spellingShingle Fernanda Cunha Jácome
Gabriela Cardoso Caldas
Arthur da Costa Rasinhas
Ana Luisa Teixeira de Almeida
Daniel Dias Coutinho de Souza
Amanda Carlos Paulino
Marcos Alexandre Nunes da Silva
Ortrud Monika Barth
Flávia Barreto dos Santos
Debora Ferreira Barreto-Vieira
Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
Pathogens
dengue 2
Asian/American lineages
BALB/c mice
kidney
histopathology and transmission electron microscopy
title Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
title_full Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
title_fullStr Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
title_full_unstemmed Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
title_short Brazilian Dengue Virus Type 2-Associated Renal Involvement in a Murine Model: Outcomes after Infection by Two Lineages of the Asian/American Genotype
title_sort brazilian dengue virus type 2 associated renal involvement in a murine model outcomes after infection by two lineages of the asian american genotype
topic dengue 2
Asian/American lineages
BALB/c mice
kidney
histopathology and transmission electron microscopy
url https://www.mdpi.com/2076-0817/10/9/1084
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