title: Signaling through the prostaglandin I2 receptor IP protects against respiratory syncytial virus-induced illness.
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.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Mark W
authors.initials: MW
authors.lastname: Geraci
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: Karine
authors.initials: K
authors.lastname: Egan
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Jamye F
authors.initials: JF
authors.lastname: O'Neal
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Russell K
authors.initials: RK
authors.lastname: Durbin
authors.forename: Peter F
authors.initials: PF
authors.lastname: Wright
authors.forename: Robert D
authors.initials: RD
authors.lastname: Collins
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzutani
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007371:Interferon-gamma / Q000032:analysis; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis; D044006:Receptors, Epoprostenol / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D015398:Signal Transduction; D015431:Weight Loss
chemical_list: D000914:Antibodies, Viral; D016898:Interferon-alpha; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D044006:Receptors, Epoprostenol; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase