title: Impaired innate host defense causes susceptibility to respiratory virus infections in cystic fibrosis.
abstract: Viral infection is the primary cause of respiratory morbidity in cystic fibrosis (CF) infants. Here, we identify that host factors allow increased virus replication and cytokine production, providing a mechanism for understanding the severity of virus disease in CF. Increased virus is due to lack of nitric oxide synthase 2 (NOS2) and 2', 5' oligoadenylate synthetase (OAS) 1 induction in response to virus or IFNgamma. This can be attributed to impairment of activation of signal transducer and activator of transcription (STAT)1, a fundamental component to antiviral defense. NO donor or NOS2 overexpression provides protection from virus infection in CF, suggesting that NO is sufficient for antiviral host defense in the human airway and is one strategy for antiviral therapy in CF children.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: De
authors.forename: Suresh
authors.initials: S
authors.lastname: Choudhary
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Tannishia
authors.initials: T
authors.lastname: Goggans
authors.forename: Roger
authors.initials: R
authors.lastname: Slee
authors.forename: Bryan R G
authors.initials: BR
authors.lastname: Williams
authors.forename: Joseph
authors.initials: J
authors.lastname: Pilewski
authors.forename: S Jaharul
authors.initials: SJ
authors.lastname: Haque
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology* / Q000821:virology*; D004198:Disease Susceptibility / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010224:Parainfluenza Virus 3, Human; D010253:Respirovirus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D020030:Nitric Oxide Donors; D014157:Transcription Factors; D007372:Interferons; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II