Neural mechanisms of respiratory syncytial virus-induced inflammation and prevention of respiratory syncytial virus sequelae.

Abstract

Respiratory syncytial virus (RSV) belongs to the paramyxovirus family and is made of a single strand of RNA encoding 10 proteins, the most important of which in terms of infectivity are the two surface glycoproteins, G and F. The G protein mediates attachment of the virus to host cells, while the F (fusion) protein mediates viral penetration and subsequent spread to adjacent respiratory epithelial cells, with fusion of cell membranes and formation of syncytia (1). The resulting infection is an extremely common, self-limited disease among infants. What is most intriguing about RSV lower respiratory tract infection, however, is the risk of persistent, recurrent wheezing, especially during the first years after the original infection. Although the frequency of this postbronchiolitic wheezing declines with age, a significant proportion of children continue to experience recurrent episodes of wheezing up to 7 to 11 yr later (2, 3). Beyond the first decade of life there no longer appears to be a significant relationship between RSV bronchiolitis and recurrent wheezing (2). Therefore, although RSV bronchiolitis may not cause lifelong respiratory problems, it appears to be associated with prolonged respiratory morbidity during the developmental years of life. RSV bronchiolitis in infancy is also associated with changes in pulmonary function. Because these changes are reversible, it is likely that they reflect a transient dysfunction of the airway control mechanisms rather than permanent remodeling. Some authors have proposed that the respiratory dysfunction following RSV bronchiolitis may be, at least in part, the result of changes in the neural pathways to the airways (4). Others believe that there is an alteration of the local immune response (5). It is possible that these two potential mechanisms are linked, with combined neuroimmune responses leading to persistent airway inflammation and hyperreactivity.