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

Fernanda Cunha Jácome,Flávia Barreto Dos Santos,Amanda Carlos Paulino,Gabriela Cardoso Caldas,Arthur Da Costa Rasinhas,Ortrud Monika Barth,Daniel Dias Coutinho De Souza,Debora Ferreira Barreto-Vieira,Marcos Alexandre Nunes Da Silva,Ana Luisa Teixeira De Almeida

doi:10.3390/pathogens10091084

Fernanda Cunha Jácome, Flávia Barreto Dos Santos + Show 8 more

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https://doi.org/10.3390/pathogens10091084

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Journal: Pathogens	Publication Date: Aug 26, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Fundação Oswaldo Cruz

Abstract

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.

Highlights

Since the DENV infection outcome can be affected by the virulence of different strains [47], and dengue related histopathological data on kidney is still scarce, here we aimed to investigate the renal involvement of BALB/c mice after infection with two distinct
A slight increase in the mean weight of the kidney of infected mice was observed when those were infected by both Lineages of Dengue virus type 2 (DENV-2) Asian/American genotype, when compared to the uninfected mice (mean = 0.423 g/standard deviation (±) = 0.06)
In individuals infected by Lineage II, there was an increase in the mean organ weight at all times of infection: at 72 hpi, the mean weight was 0.43 ± 0.06 g, at 7 dpi, 0.468 ± 0.04 g and at 14 dpi, 0.477 ± 0.04 g

Summary

Introduction

Dengue virus serotypes 1 to 4 (DENV-1–4) are arboviruses belonging to the genus. Flavivirus of the family Flaviviridae [1]. Transmission occurs in over 125 countries and around 4 billion people are at risk of infection annually [2]. Dengue poses a major threat to urban populations in Asia and Latin America, mainly due to its increased incidence in the last 50 years [3,4,5]. In Brazil, Lineage I of DENV-2 Asian/American genotype has been circulating since the 1990’s [6], when the first cases of dengue haemorrhagic fever and dengue shock syndrome (DHF/DSS) were reported [7]. After 17 years, the emergence of Lineage II of DENV-2 Asian/American genotype was associated with increased disease

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