Anionic Pulmonary Surfactant Lipids Suppress Respiratory Syncytial Virus Infection

摘要

The changes in surfactant phospholipids of lungs, especially the minor surfactant phospholipids, palmitoyl-oleoyl-phosphatidyl-glycerol (POPG), correlates with the pathogenesis of pulmonary diseases, acute respiratory disease (ARDS), interstitial lung disease (ILD), and bronchial asthma. We have recently discovered that POPG has broad inhibitory effects on proin-flammatory cytokine production (IL-6, IL-8) induced by multiple TLR agonists (TLR1/2, TLR3, TLR4, TLR2/6, TLR7/8) in bronchial epithelium. Respiratory syncytial virus (RSV) is the most common cause of hospitalization for respiratory illness in young children and RSV infection is one major cause of acute exacerbation of asthma. The aim of this study was to determine the function of surfactant lipids, especially POPG, to RSV infection. We estimated the effects of POPG on human bronchial epithelial cells (Beas2B and primary cells [NHBE]), with RSV infection. Pretreatment with POPG significantly blocked viral infection and proinflammatory cytokine (IL-6, IL-8) production and cytopathic effects induced by RSV in bronchial epithelial cells. Direct binding measurements showed that RSV interacts with CD 14, and POPG markedly inhibits this interaction by binding both virus and the protein. To determine POPG has inhibitory effects in vivo, we infected BALB/c mice with RSV. POPG treatment markedly attenuated RSV titer in the lung and lung inflammation in histopathology. These findings demonstrate a potent anti RSV function for POPG and raise the possibility of its use to treat infections and pulmonary disease.