Secondary infection with dengue viruses in a murine model: morphological analysis

DÃ©bora Ferreira Barreto-Vieira; Christina Maeda Takiya; Fernanda Cunha JÃ¡come; Arthur da Costa Rasinhas; Ortrud Monika Barth

Volume : V, Issue : VI, June - 2015

Secondary infection with dengue viruses in a murine model: morphological analysis

D Bora Ferreira Barreto 45 Vieira, Christina Maeda Takiya, Fernanda Cunha J Come, Arthur Da Costa Rasinhas, Ortrud Monika Barth

Abstract :

Morphological alterations in the lungs, liver and heart of BALB/c mice reinfected intravenously with heterologous dengue virus (DENV) using non–neuroadapted DENV serotypes 1 and 2 were analysed. Tissues samples were processed using the standard techniques of photonic and transmission electron microscopy. Morphological observations of lung tissue showed eakdown of the alveolocapillary barrier leading to alveolitis, focal zones of collapse, and intraalveolar haemorrhage. Inside alveolar septa, congested capillaries contained inflammatory cells and platelets. Alveolar capillary endothelial cells exhibited aspects of activation with protruding phyllopod and intracytoplasmic vesicles and vacuoles. The liver exhibited vacuolisation of hepatocytes, inflammatory cells inside sinusoidal capillaries, enlargement of sinusoidal capillaries, foci of haemorrhage inside the interstitium, oedema in the peri–centrilobular vein space and the presence of phyllopods and pseudopod–like extensions in endothelial cells. In heart tissue, a slight loss of cytoplasm in cardiac cells, which are areas with inflammatory infiltrate, and the presence of phyllopods in endothelial cells and the disorganisation of cardiac fies were observed. DENV particles, DENV–specific antigen and DENV RNA were observed in mosquito cell (C6/36) cultures inoculated with the sera of reinfected animals. The morphological alterations observed in lung, liver and heart tissue were similar to what has been observed in human cases of dengue and severe dengue fever. The present study demonstrates that BALB/c mice reinfected with a heterologous serotype of DENV in this model develop more severe lesions than those observed in mice during primary infection.