title: Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection.
abstract: Respiratory syncytial virus (RSV) causes respiratory tract infections in young children, and significant morbidity and mortality in the elderly, immunosuppressed, and immunocompromised patients and in patients with chronic lung diseases. Recently, we reported that the pulmonary surfactant phospholipid palmitoyl-oleoyl-phosphatidylglycerol (POPG) inhibited RSV infection in vitro and in vivo by blocking viral attachment to epithelial cells. Simultaneous application of POPG along with an RSV challenge to mice markedly attenuated infection and associated inflammatory responses. Based on these findings, we expanded our studies to determine whether POPG is effective for prophylaxis and postinfection treatment for RSV infection. In vitro application of POPG at concentrations of 0.2-1.0 mg/ml at 24 h after RSV infection of HEp-2 cells suppressed interleukin-8 production up to 80% and reduced viral plaque formation by 2-6 log units. In vivo, the turnover of POPG in mice is relatively rapid, making postinfection application impractical. Intranasal administration of POPG (0.8-3.0 mg), 45 min before RSV inoculation in mice reduced viral infection by 1 log unit, suppressed inflammatory cell appearance in the lung, and suppressed virus-elicited interferon-γ production. These findings demonstrate that POPG is effective for short-term protection of mice against subsequent RSV infection and that it has potential for application in humans.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO.
authors.forename: Mari
authors.initials: M
authors.lastname: Numata
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado - Denver, Aurora, CO; and.
authors.forename: Karin Z
authors.initials: KZ
authors.lastname: Berry
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO.
authors.forename: Mallory
authors.initials: M
authors.lastname: Chan
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO.
authors.forename: Pitchaimani
authors.initials: P
authors.lastname: Kandasamy
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado - Denver, Aurora, CO; and.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO. Electronic address: voelkerd@njhealth.org.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018890:Chemoprevention; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010715:Phosphatidylglycerols / Q000627:therapeutic use*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D016209:Interleukin-8; D010715:Phosphatidylglycerols
keywords: antiviral; innate immunity; pulmonary surfactant