Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection
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 phospholip...
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doaj-d91be74b105d4d9496af1ecf380f163e2021-04-28T06:02:11ZengElsevierJournal of Lipid Research0022-22752013-08-0154821332143Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infectionMari Numata0Yoji Nagashima1Martin L. Moore2Karin Z. Berry3Mallory Chan4Pitchaimani Kandasamy5R. Stokes Peebles, Jr.6Robert C. Murphy7Dennis R. Voelker8Department of Medicine, National Jewish Health, Denver, CODepartment of Pathology, Yokohama City University School of Medicine, Yokohama, JapanEmory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GADepartment of Pharmacology, School of Medicine, University of Colorado - Denver, Aurora, CO; andDepartment of Medicine, National Jewish Health, Denver, CODepartment of Medicine, National Jewish Health, Denver, CODepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TNDepartment of Pharmacology, School of Medicine, University of Colorado - Denver, Aurora, CO; andTo whom correspondence should be addressed; Department of Medicine, National Jewish Health, Denver, CORespiratory 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.http://www.sciencedirect.com/science/article/pii/S0022227520375295antiviralinnate immunitypulmonary surfactant |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mari Numata Yoji Nagashima Martin L. Moore Karin Z. Berry Mallory Chan Pitchaimani Kandasamy R. Stokes Peebles, Jr. Robert C. Murphy Dennis R. Voelker |
spellingShingle |
Mari Numata Yoji Nagashima Martin L. Moore Karin Z. Berry Mallory Chan Pitchaimani Kandasamy R. Stokes Peebles, Jr. Robert C. Murphy Dennis R. Voelker Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection Journal of Lipid Research antiviral innate immunity pulmonary surfactant |
author_facet |
Mari Numata Yoji Nagashima Martin L. Moore Karin Z. Berry Mallory Chan Pitchaimani Kandasamy R. Stokes Peebles, Jr. Robert C. Murphy Dennis R. Voelker |
author_sort |
Mari Numata |
title |
Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
title_short |
Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
title_full |
Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
title_fullStr |
Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
title_full_unstemmed |
Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
title_sort |
phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2013-08-01 |
description |
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. |
topic |
antiviral innate immunity pulmonary surfactant |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520375295 |
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