Abstract
The role of prostanoids in modulating respiratory syncytial virus (RSV) infection is unknown. We found that RSV infection in mice increases production of prostaglandin I(2) (PGI(2)). Mice that overexpress PGI(2) synthase selectively in bronchial epithelium are protected against RSV-induced weight loss and have decreased peak viral replication and gamma interferon levels in the lung compared to nontransgenic littermates. In contrast, mice deficient in the PGI(2) receptor IP have exacerbated RSV-induced weight loss with delayed viral clearance and increased levels of gamma interferon in the lung compared to wild-type mice. These results suggest that signaling through IP has antiviral effects while protecting against RSV-induced illness and that PGI(2) is a potential therapeutic target in the treatment of RSV.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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6-Ketoprostaglandin F1 alpha / analogs & derivatives*
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6-Ketoprostaglandin F1 alpha / urine
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Animals
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Antibodies, Viral / blood
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism
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Disease Models, Animal
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Epoprostenol / metabolism*
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Female
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Gene Deletion
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Interferon-alpha / biosynthesis
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Interferon-beta / biosynthesis
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Interferon-gamma / analysis
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / metabolism
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Lung / chemistry
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Lung / pathology
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Lung / virology
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Male
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Mice
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Mice, Transgenic
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Pulmonary Edema / pathology
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Pulmonary Edema / prevention & control
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Pulmonary Surfactant-Associated Protein A / biosynthesis
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Pulmonary Surfactant-Associated Protein B / biosynthesis
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Receptors, Epoprostenol / genetics
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Receptors, Epoprostenol / immunology
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Receptors, Epoprostenol / metabolism*
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Respiratory Mucosa
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Respiratory Syncytial Virus Infections / immunology
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Respiratory Syncytial Virus Infections / metabolism
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Respiratory Syncytial Virus Infections / pathology
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Respiratory Syncytial Virus Infections / physiopathology*
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Respiratory Syncytial Viruses / growth & development
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Respiratory Syncytial Viruses / immunology
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Respiratory Syncytial Viruses / pathogenicity*
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Signal Transduction*
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Weight Loss
Substances
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Antibodies, Viral
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Interferon-alpha
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Protein B
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Receptors, Epoprostenol
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6-Ketoprostaglandin F1 alpha
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2,3-dinor-6-ketoprostaglandin F1alpha
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Interferon-beta
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Interferon-gamma
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Cytochrome P-450 Enzyme System
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Epoprostenol
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Intramolecular Oxidoreductases
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prostacyclin synthetase