Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model

Abstract Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue...

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Autores principales:	Fernanda Cunha Jácome, Gabriela Cardoso Caldas, Arthur da Costa Rasinhas, Ana Luisa Teixeira de Almeida, Daniel Dias Coutinho de Souza, Amanda Carlos Paulino, Raphael Leonardo, Ortrud Monika Barth, Flavia Barreto dos Santos, Débora Ferreira Barreto-Vieira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb22953373df4be4928af5add086f2e5
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spelling	oai:doaj.org-article:cb22953373df4be4928af5add086f2e52021-12-02T14:49:33ZComparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model10.1038/s41598-021-88502-22045-2322https://doaj.org/article/cb22953373df4be4928af5add086f2e52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88502-2https://doaj.org/toc/2045-2322Abstract Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.Fernanda Cunha JácomeGabriela Cardoso CaldasArthur da Costa RasinhasAna Luisa Teixeira de AlmeidaDaniel Dias Coutinho de SouzaAmanda Carlos PaulinoRaphael LeonardoOrtrud Monika BarthFlavia Barreto dos SantosDébora Ferreira Barreto-VieiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernanda Cunha Jácome Gabriela Cardoso Caldas Arthur da Costa Rasinhas Ana Luisa Teixeira de Almeida Daniel Dias Coutinho de Souza Amanda Carlos Paulino Raphael Leonardo Ortrud Monika Barth Flavia Barreto dos Santos Débora Ferreira Barreto-Vieira Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
description	Abstract Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.
format	article
author	Fernanda Cunha Jácome Gabriela Cardoso Caldas Arthur da Costa Rasinhas Ana Luisa Teixeira de Almeida Daniel Dias Coutinho de Souza Amanda Carlos Paulino Raphael Leonardo Ortrud Monika Barth Flavia Barreto dos Santos Débora 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 Raphael Leonardo Ortrud Monika Barth Flavia Barreto dos Santos Débora Ferreira Barreto-Vieira
author_sort	Fernanda Cunha Jácome
title	Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
title_short	Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
title_full	Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
title_fullStr	Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
title_full_unstemmed	Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
title_sort	comparative analysis of liver involvement caused by two denv-2 lineages using an immunocompetent murine model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cb22953373df4be4928af5add086f2e5
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Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model

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