Dados do Trabalho

Título

Hepatic damage in secondary dengue infection: histological and ultrastructural aspects of a murine model

Introdução

Dengue is widely spread in tropical and subtropical regions, and epidemiological studies suggest that more severe cases are associated with secondary heterologous infection and with certain dengue virus (DENV) serotypes, the DENV-2 and DENV-3. Hepatic alterations are common in dengue and understanding the pattern of damage in this target organ enables correlation to general mechanisms of DENV systemic infection.

Objetivo (s)

This study aimed to evaluate the impact of secondary infection with non-neuroadapted clinical DENV strains on the morphological profile of liver of immunocompetent mice.

Material e Métodos

For this purpose, two-month-old BALB/cJ mice were infected with 10^4 PFU of DENV-3 and, two months later, infected with 10^4 PFU of DENV-2, by intravenous route. Five animals were analyzed by time of infection and the negative control group was MOCK-inoculated. After 3, 7, 10, 14 or 21 days after infection (DAI), mice were euthanized, liver was collected and processed for analysis by both bright field and transmission electron microscopies. Histomorphometry parameters were evaluated in 30 fields per animal and included counting uni-/binucleated hepatocytes and measuring the luminal area of liver sinusoid capillaries.

Resultados e Conclusão

Hepatocellular necrosis, hydropic degeneration, microsteatosis, vascular congestion, foci of inflammatory infiltrate and reactive hepatocytes were observed. Morphological alterations occurred in all times of infection. The mice at 10 DAI showed most changes and the highest values of hepatocytes, binucleation and sinusoidal dilation. Despite the severity of certain alterations, a degree of recovery from the injuries was observed in the last times of infection, specially at 21 DAI. In addition to corroborating alterations observed in bright field microscopy, ultrastructural analysis of the liver parenchyma also showed elevated autophagy in hepatocytes and changes in endothelial cells, such as activation, evidenced by the emission of membrane extensions, projection into the lumen of the blood vessel and intense transit of cytoplasmic vesicles. According to our analyses, the location of tissue damage appears to be important for the overall picture in the organ, and autophagy could be a significant way to improve viral fitness or indirect injuries.

Palavras Chave

dengue; secondary infection; murine model; liver