Respiratory Syncytial Virus Persistence in the Lungs Correlates with Airway Hyperreactivity in the Mouse Model

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization in infants and young children worldwide [1, 2]. In addition to the acute morbidity [3], the association between RSV lower respiratory tract infection and the development of recurrent wheezing has been clearly established in several well-controlled prospective studies [4–7]. In fact, among children hospitalized for RSV bronchiolitis, studies indicate that >30% will develop persistent wheezing until 13 years of age, which may extend into early adulthood [4, 5]. The nature of this association is not well understood, and both the host and the virus likely contribute to the development of RSV-induced long-term airway disease [8, 9]. Recent evidence derived from in vitro experiments [10], animal models [11–14], and studies in adults [15] suggests that RSV may persist “latently” or at a low level of viral replication in immunologically privileged sites in the lung, avoiding immune detection and elimination [16]. However, questions have arisen regarding the significance, if any, of RSV persistence. This study was designed to characterize the significance of RSV RNA persistence in the lungs by using a mouse model of RSV infection. To this end, we determined whether the establishment of RSV RNA persistence in the lungs required active viral replication and whether RSV RNA persistence correlated with the development of RSV-induced chronic pulmonary disease.