Respiratory reovirus 1/L induction of diffuse alveolar damage: a model of acute respiratory distress syndrome.

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that is characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. In this report we describe a unique animal model in which CBA/J mice infected with reovirus serotype 1, strain Lang develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consists of the overlapping phases of exudation including the formation of hyaline membranes, regeneration, and healing via resolution and/or repair with fibrosis. While the consequences of a number of infectious and noninfectious insults in various animal systems have been developed as models of human ARDS, they are models of acute lung injury and are of short-term duration. Therefore, they do not recapitulate all of the clinical and pathological phases observed in human ARDS. Thus, study of the cellular and molecular factors involved in these distinct phases of the disease have been limited. Reovirus 1/L infection of CBA/J mice will allow investigations of the pathophysiology of ARDS as it progresses from the initial stages of edema and neutrophilia to fibrotic lesion development in late stages.