Respiratory Syncytial Virus Infections: Old Challenges and New Opportunities

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Abstract
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among children aged < 1 year. The majority of children hospitalized for RSV infection are younger than 6 months of age. RSV also causes repeated infections including severe lower respiratory tract disease, which may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems. Using the mouse model of RSV infection, this article examines the immunopathogenesis during acute and chronic phases of the disease. This model allows for measurement of basal enhanced pause, which reflects airway obstruction in the acute phase, and the response to methacholine challenge to assess airway hyperresponsiveness during the chronic phase. This article also summarizes some recent studies focusing on novel perspectives and strategies for treatment and prevention of RSV infections. Compared with the lungs of sham-inoculated control mice, mice inoculated with live RSV showed a persistent progression of the severity of pneumonia as determined by an increasing histopathologic score. Mucus production of RSV-infected mice in the acute phase illustrated increased periodic acid-Schiff-positive hypertrophic cells in central and peripheral airways. RSV-infected mice with persistent airway hyperresponsiveness exhibited the presence of abnormal chronic inflammatory changes and mucus overproduction, which likely contributed to long term airway disease induced by RSV infection. These findings provide a histologic correlation to the abnormal pulmonary responses documented by plethysmography. Current trials have demonstrated positive results in continuing to target different alternatives for a new RSV vaccine.