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

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.

Emergence of a new variant of dengue virus serotype 2 in Jazan region, southwestern Saudi Arabia

“…Although the effect of genetic diversity between DENV serotypes and genotypes on clinical outcome is still controversial, the severity and endemicity of DENV have been linked to new variants in outbreaks in endemic areas [24,[41][42][43][44]. DENV-2 is the serotype commonly responsible for large epidemics in Asia and Latin America, with secondary DENV-2 infection associated with more severe disease [45][46][47].…”

Virus-Associated Nephropathies: A Narrative Review

“…However, there are no current data to suggest DENV replicates in renal cells [ 253 ], and viral particles may rely on deposition of DENV antigen complexed to antibodies or primarily degraded and/or phagocyted virus [ 254 ]. Glomerular injuries have been described in animal models [ 255 ] and human studies [ 256 ], notably with FSGS [ 257 , 258 ] and MPGN [ 259 ], without correlation with the APOL-1 risk allele but with demonstrated infection in the kidney tissues. Finally, thrombotic microangiopathy has also been reported [ 260 , 261 ].…”

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

“…Immunocompetent mice, including BALB/c, have been used for DENV pathogenesis and tropism studies by using different infection routes, and clinical signs as well as tissue alterations similar to those observed in dengue human cases were observed, even using epidemic non-adapted DENV strains. Viral genomes and antigens have been detected in the spleen, liver, brain, heart, lung, kidney and saliva [38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Moreover, BALB/c was recently shown to be useful in a therapeutic approach to treat DENV infection with improved tissue repair and regeneration [52].…”