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Background: Dengue is a disease caused by dengue virus (DENV-1 through -4). Among the four serotypes, DENV-4 remains the least studied. Acute kidney injury is a potential complication of dengue generally associated with severe dengue infection., Objectives: The goal of this study was to investigate the alterations caused by experimental dengue infection in the kidney of adult BALB/c mice., Methods: In this study, BALB/c mice were infected through the intravenous route with a DENV-4 strain, isolated from a human patient. The kidneys of the mice were procured and subject to histopathological and ultrastructural analysis., Findings: The presence of the viral antigen was confirmed through immunohistochemistry. Analysis of tissue sections revealed the presence of inflammatory cell infiltrate throughout the parenchyma. Glomerular enlargement was a common find. Necrosis of tubular cells and haemorrhage were also observed. Analysis of the kidney on a transmission electron microscope allowed a closer look into the necrotic tubular cells, which presented nuclei with condensed chromatin, and loss of cytoplasm., Main Conclusions: Even though the kidney is probably not a primary target of dengue infection in mice, the inoculation of the virus in the blood appears to damage the renal tissue through local inflammation.

Despite the advancement of molecular biology techniques, morphological studies using transmission electron microscopy (TEM) are still being of great importance to elucidate some aspects of viral structures, morphogenesis, and pathogenesis. In relation to dengue viruses (DENV), several studies report the use of TEM to obtain a clearer definition of viral morphology, the events involved in its morphogenesis, aspects of pathogenesis, and cell tropism. In this chapter, the main technical protocols and their respective reagents for studies of DENV infection by TEM are described, both in cell culture and in biological tissue samples., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Dengue, considered the most important arthropod-borne viral disease affecting humans, is transmitted by the bite of mosquitoes of the genus Aedes and caused by one of the four distinct serotypes of dengue virus (DENV-1, -2, -3 and -4). Infection with one of the four serotypes provides lifelong homotypic immunity. However, immunity against the heterologous serotypes is transient. As a consequence, secondary infection may lead to severer manifestations due to cross-reactivity of antibodies and T-cells. Over 500,000 people are hospitalized every year and around 2,5 million, living in endemic areas, are at risk of infection. Given the background, the development of vaccines and anti-DENV drugs is of the utmost importance, as is the characterization of an animal model for testing them. The purpose of this study was to investigate ultrastructural alterations caused by DENV secondary infection in BALB/c mice heart. To achieve our goal, six BALB/c mice were infected with DENV-1 and, 4 months later, reinfected with DENV-2. Uninfected mice were used as negative controls. Heart samples were collected and processed for ultrastructural and histopathological analysis. Our results showed edema, endothelium activation characterized by the presence of transport vesicles, free platelets in interstitium, mitochondria presenting rarefied matrix and degenerated cristae, and disorganization of muscle fibers. These results point not only to BALB/c mice susceptibility to DENV infection, but also to the fact that, although it is not an often reported occurrence, dengue can lead to heart damage. Keywords: dengue; experimental model; reinfection; BALB/c mice.

The lack of an experimental animal model for the study of dengue pathogenesis is a limiting factor for the development of vaccines and drugs. In previous studies, our group demonstrated the susceptibility of BALB/c mice to infection by dengue virus (DENV) 1 and 2, and the virus was successfully isolated in several organs. In this study, BALB/c mice were experimentally infected intravenously with DENV-4, and samples of their saliva were collected. Viral RNA extracted from the saliva samples was subjected to qRT-PCR, with a detection limit of 0.002 PFU/mL. The presence of DENV-4 viral RNA was detected in the saliva of two mice, presenting viral titers of 109 RNA/mL. The detection of DENV RNA via saliva sampling is not a common practice in dengue diagnosis, due to the lower detection rates in human patients. However, the results observed in this study seem to indicate that, as in humans, detection rates of DENV RNA in mouse saliva are also low, correlating the infection in both cases. This study reports the first DENV detection in the saliva of BALB/c immunocompetent mice experimentally infected with non-neuroadapted DENV-4.