Histopathological aspects of Dengue-2 virus infected mice tissues and complementary virus isolation

The difficulty in studying dengue virus (DENV) infection in humans and in developing a virus vaccine is the absence of a suitable animal model which develops the full spectra of the Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Despite the fact that viruses have been found in various animal tissues, we isolated DENV from tissues of adult BALB/c mice, inoculated with DENV serotype 2 (DENV-2) obtained from human serum. Viruses were ultrastructurally identified and immunolocalized by immunofluorescence techniques in C6/36 mosquito cell cultures, inoculated with tissues (liver, lung, kidney and cerebellum) macerate supernatant from mice, 48 h post-infection (p.i.). These organs, collected at the same stage of infection, were examined histologically. The histopathological analysis revealed focal alterations in all tissues examined. Liver contained focal ballooned hepatocytes, but without modifying the average diameter of the majority of hepatocytes. Sinusoidal lumen was significantly diminished at this stage but portal and centrolobular veins became congested. Lungs exhibited hemorrhagic foci in the alveolar space, vascular congestion and focal alveolitis. Cerebellar tissue showed rare foci of neuronal compactation (Purkinje cells) and perivascular oedema. In kidneys it was observed an increase in glomerular volume with augmented endocapillary and mesangial cellularity, with reactivity to anti-IgM in all glomeruli of infected mice. In conclusion, DENV-2 was found in all tissues examined early in the evolution of infection. Presence of viruses in tissues has mainly led to hemodynamic alterations with generalized vascular congestion and increased permeability, and mast cell recruitment in lungs. The latter could participate in the vascular modifications in tissues.