Respiratory syncytial virus-induced oxidative stress in lung pathogenesis

Abstract

Respiratory viral infections remain the major cause of severe lower respiratory tract disease in both children and adults worldwide. Respiratory syncytial virus (RSV) is a negative-sense single-stranded RNA virus of the family Pneumoviridae, which is responsible for acute lower respiratory tract infections (LRTI) in children and is a major cause of severe respiratory morbidity and mortality in the elderly and immunocompromised. These LRTI in young children are often characterized by wheezing and are defined as "bronchiolitis. "RSV bronchiolitis in infancy is strongly associated with the subsequent development of asthma and other forms of bronchial disease. Currently, there is no effective vaccine or specific therapy available for RSV infection, and natural immunity is inadequate, resulting in reinfections through adulthood. The high risk of recurrence and mortality rates of respiratory viral infections in young children and the elderly explains the importance for continuing efforts to understand the pathogenesis of respiratory virus-induced lung inflammation in order to design better therapeutic strategies. Lung epithelial cells are the major targets of RSV infection and play a central role in orchestrating the response to oxidative stress. Although the pathogenic mechanisms of RSV-induced acute airway disease and associated long-term consequences are still unclear, experimental evidence suggests that early inflammatory and immune events in the lung play a fundamental role in the outcome of the disease. Moreover, oxidative stress plays an important role in the pathogenesis of many inflammatory lung diseases including asthma and chronic obstructive pulmonary disease. Studies have shown that the oxidative stress response in the airways, which results from an imbalance between reactive oxygen species (ROS) production and lung antioxidant defenses, plays a major role in the pathogenesis of RSV-associated lung inflammatory disease as RSV induces excess oxidant production and inhibits antioxidant enzymes expression. Studies have also demonstrated the role of ROS as important intracellular messengers of RSV-induced cellular signaling leading to the expression of key proinflammatory mediators, such as cytokines and chemokines. This chapter reviews the various mechanisms of RSV-induced oxidative stress and associated pathogenicity. Specifically, we will focus on recent studies demonstrating the role of ROS as important regulators of respiratory virus-induced cellular signaling and inflammatory responses induced as a result of RSV-induced oxidative stress.