Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle

Dengue virus (DENV) infection by one of the four serotypes (DENV-1 to 4) may result in a wide spectrum of clinical manifestations, with unpredictable evolution and organ involvement. Due to its association with severe epidemics and clinical manifestations, DENV-2 has been substantially investigated....

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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, Derick Mendes Bandeira, Ortrud Monika Barth, Flavia Barreto dos Santos, Debora Ferreira Barreto-Vieira
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/9/12/2536
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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
Derick Mendes Bandeira
Ortrud Monika Barth
Flavia 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
Derick Mendes Bandeira
Ortrud Monika Barth
Flavia Barreto dos Santos
Debora Ferreira Barreto-Vieira
author_sort Fernanda Cunha Jácome
collection DOAJ
description Dengue virus (DENV) infection by one of the four serotypes (DENV-1 to 4) may result in a wide spectrum of clinical manifestations, with unpredictable evolution and organ involvement. Due to its association with severe epidemics and clinical manifestations, DENV-2 has been substantially investigated. In fact, the first emergence of a new lineage of the DENV-2 Asian/American genotype in Brazil (Lineage II) in 2008 was associated with severe cases and increased mortality related to organ involvement. A major challenge for dengue pathogenesis studies has been a suitable animal model, but the use of immune-competent mice, although sometimes controversial, has proven to be useful, as histological observations in infected animals reveal tissue alterations consistent to those observed in dengue human cases. Here, we aimed to investigate the outcomes caused by two distinct lineages of the DENV-2 Asian/American genotype in the lung, heart and skeletal muscle tissues of infected BALB/c mice. Tissues were submitted to histopathology, immunohistochemistry, histomorphometry and transmission electron microscopy (TEM) analysis. The viral genome was detected in heart and skeletal muscle samples. The viral antigen was detected in cardiomyocytes and endothelial cells of heart tissue. Heart and lung tissue samples presented morphological alterations comparable to those seen in dengue human cases. Creatine kinase serum levels were higher in mice infected with both lineages of DENV-2. Additionally, statistically significant differences, concerning alveolar septa thickening and heart weight, were observed between BALB/c mice infected with both DENV-2 lineages, which was demonstrated to be an appropriate experimental model for dengue pathogenesis studies on lung, heart and skeletal muscle tissues.
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spelling doaj.art-1cdd2147ab464f2b8f91698bf0994bf12023-11-23T09:39:29ZengMDPI AGMicroorganisms2076-26072021-12-01912253610.3390/microorganisms9122536Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal MuscleFernanda Cunha Jácome0Gabriela Cardoso Caldas1Arthur da Costa Rasinhas2Ana Luisa Teixeira de Almeida3Daniel Dias Coutinho de Souza4Amanda Carlos Paulino5Marcos Alexandre Nunes da Silva6Derick Mendes Bandeira7Ortrud Monika Barth8Flavia Barreto dos Santos9Debora Ferreira Barreto-Vieira10Laboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Immunology, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilLaboratory of Viral Morphology and Morphogenesis, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Rio de Janeiro 21040-900, BrazilDengue virus (DENV) infection by one of the four serotypes (DENV-1 to 4) may result in a wide spectrum of clinical manifestations, with unpredictable evolution and organ involvement. Due to its association with severe epidemics and clinical manifestations, DENV-2 has been substantially investigated. In fact, the first emergence of a new lineage of the DENV-2 Asian/American genotype in Brazil (Lineage II) in 2008 was associated with severe cases and increased mortality related to organ involvement. A major challenge for dengue pathogenesis studies has been a suitable animal model, but the use of immune-competent mice, although sometimes controversial, has proven to be useful, as histological observations in infected animals reveal tissue alterations consistent to those observed in dengue human cases. Here, we aimed to investigate the outcomes caused by two distinct lineages of the DENV-2 Asian/American genotype in the lung, heart and skeletal muscle tissues of infected BALB/c mice. Tissues were submitted to histopathology, immunohistochemistry, histomorphometry and transmission electron microscopy (TEM) analysis. The viral genome was detected in heart and skeletal muscle samples. The viral antigen was detected in cardiomyocytes and endothelial cells of heart tissue. Heart and lung tissue samples presented morphological alterations comparable to those seen in dengue human cases. Creatine kinase serum levels were higher in mice infected with both lineages of DENV-2. Additionally, statistically significant differences, concerning alveolar septa thickening and heart weight, were observed between BALB/c mice infected with both DENV-2 lineages, which was demonstrated to be an appropriate experimental model for dengue pathogenesis studies on lung, heart and skeletal muscle tissues.https://www.mdpi.com/2076-2607/9/12/2536dengue virus serotype 2lineagesBALB/c micelungheartskeletal muscle
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
Derick Mendes Bandeira
Ortrud Monika Barth
Flavia Barreto dos Santos
Debora Ferreira Barreto-Vieira
Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
Microorganisms
dengue virus serotype 2
lineages
BALB/c mice
lung
heart
skeletal muscle
title Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
title_full Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
title_fullStr Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
title_full_unstemmed Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
title_short Immunocompetent Mice Infected by Two Lineages of Dengue Virus Type 2: Observations on the Pathology of the Lung, Heart and Skeletal Muscle
title_sort immunocompetent mice infected by two lineages of dengue virus type 2 observations on the pathology of the lung heart and skeletal muscle
topic dengue virus serotype 2
lineages
BALB/c mice
lung
heart
skeletal muscle
url https://www.mdpi.com/2076-2607/9/12/2536
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