title: Phosphatidylinositol inhibits respiratory syncytial virus infection.
abstract: Respiratory syncytial virus (RSV) infects nearly all children under age 2, and reinfection occurs throughout life, seriously impacting adults with chronic pulmonary diseases. Recent data demonstrate that the anionic pulmonary surfactant lipid phosphatidylglycerol (PG) exerts a potent antiviral effect against RSV in vitro and in vivo. Phosphatidylinositol (PI) is also an anionic pulmonary surfactant phospholipid, and we tested its antiviral activity. PI liposomes completely suppress interleukin-8 production from BEAS2B epithelial cells challenged with RSV. The presence of PI during viral challenge in vitro reduces infection by a factor of >10(3). PI binds RSV with high affinity, preventing virus attachment to epithelial cells. Intranasal inoculation with PI along with RSV in mice reduces the viral burden 30-fold, eliminates the influx of inflammatory cells, and reduces tissue histopathology. Pharmacological doses of PI persist for >6 h in mouse lung. Pretreatment of mice with PI at 2 h prior to viral infection effectively suppresses inflammation and reduces the viral burden by 85%. These data demonstrate that PI has potent antiviral properties, a long residence time in the extracellular bronchoalveolar compartment, and a significant prophylaxis window. The findings demonstrate PG and PI have complementary roles as intrinsic, innate immune antiviral mediators in the lung.
authors.affiliation: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206.
authors.forename: Mari
authors.initials: M
authors.lastname: Numata
authors.affiliation: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206.
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206.
authors.forename: Rachel
authors.initials: R
authors.lastname: Fickes
authors.affiliation: Department of Pharmacology, University of Colorado, Denver, CO 80045.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO 80206. Electronic address: voelkerd@njhealth.org.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008168:Lung / Q000276:immunology*; D051379:Mice; D010716:Phosphatidylinositols / Q000494:pharmacology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
chemical_list: D010716:Phosphatidylinositols
keywords: epithelium; immunology; inflammation; innate immunity; lung; phospholipids; prophylaxis; pulmonary surfactant