HISTOPATHOLOGICAL AND ULTRASTRUCTURAL STUDIES OF LUNG TISSUE OF MICE REINFECTED WITH DENGUE VIRUS SEROTYPES 1 OR 2

Abstract

Histological and ultrastructural alterations in lung of BALB/c mice reinfected with heterologous DENV by the intravenous route with non-neuroadapted dengue viruses serotypes 1 and 2 were analyzed. The lung samples were processed following the standard techniques of photonic and transmission electron microscopy. Morphological studies showed breakdown of alveolocapilar barrier leading to alveolitis, focal zones of collapse, and intraalveolar hemorrhage. Inside alveolar septa, congested capillaries exhibited neutrophils and platelets. Alveolar capillary endothelial cells exhibited aspects of activation with exuberant phylopodia and intracytoplasmic vesicles and vacuoles. Morphometrical analyses demonstrated an increase of the surface density of interalveolar septa in all reinfected mice while alveolar space density was decreased. All these morphometrical data corroborated the histological features emphasizing the alveolocapilar breakdrown in dengue infected animals. Important is the fact that reinfection leads to intraalveolar fibrogenesis as demonstrated by histomorphometry and ultrastructural studies. DENV particles, antigens and RNA were observed 72 hours post-reinfection in mosquito cells (C6/36) inoculated with sera of the animals. The morphological alterations observed in lungs were similar to the observed in human cases of dengue fever and dengue hemorrhagic fever. The present study demonstrates that the BALB/c mice, during the secondary infection by a heterologous serotype of DENV, develop morphological alterations in lung tissue more severe than those observed in the primary infection.