title: Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide.
abstract: Recent reports postulate that the dual oxidase (DUOX) proteins function as part of a multicomponent oxidative pathway used by the respiratory mucosa to kill bacteria. The other components include epithelial ion transporters, which mediate the secretion of the oxidizable anion thiocyanate (SCN(-)) into airway surface liquid, and lactoperoxidase (LPO), which catalyzes the H(2)O(2)-dependent oxidation of the pseudohalide SCN(-) to yield the antimicrobial molecule hypothiocyanite (OSCN(-)). We hypothesized that this oxidative host defense system is also active against respiratory viruses. We evaluated the activity of oxidized LPO substrates against encapsidated and enveloped viruses. When tested for antiviral properties, the LPO-dependent production of OSCN(-) did not inactivate adenovirus or respiratory syncytial virus (RSV). However, substituting SCN(-) with the alternative LPO substrate iodide (I(-)) resulted in a marked reduction of both adenovirus transduction and RSV titer. Importantly, well-differentiated primary airway epithelia generated sufficient H(2)O(2) to inactivate adenovirus or RSV when LPO and I(-) were supplied. The administration of a single dose of 130 mg of oral potassium iodide to human subjects increased serum I(-) concentrations, and resulted in the accumulation of I(-) in upper airway secretions. These results suggest that the LPO/I(-)/H(2)O(2) system can contribute to airway antiviral defenses. Furthermore, the delivery of I(-) to the airway mucosa may augment innate antiviral immunity.
authors: Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors: Anthony J
authors: AJ
authors: Fischer
authors: Nicholas J
authors: NJ
authors: Lennemann
authors: Sateesh
authors: S
authors: Krishnamurthy
authors: Péter
authors: P
authors: Pócza
authors: Lakshmi
authors: L
authors: Durairaj
authors: Janice L
authors: JL
authors: Launspach
authors: Bethany A
authors: BA
authors: Rhein
authors: Christine
authors: C
authors: Wohlford-Lenane
authors: Daniel
authors: D
authors: Lorentzen
authors: Botond
authors: B
authors: Bánfi
authors: Paul B
authors: PB
authors: McCray
mesh_terms: D000256:Adenoviridae / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D018928:Immunity, Mucosal / Q000187:drug effects*; D017613:Iodine Compounds / Q000378:metabolism; D007784:Lactoperoxidase / Q000378:metabolism; D010084:Oxidation-Reduction; D011193:Potassium Iodide / Q000378:metabolism / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D012974:Sodium Iodide / Q000378:metabolism / Q000494:pharmacology*; D013552:Swine; D013861:Thiocyanates / Q000378:metabolism; D013997:Time Factors; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D017613:Iodine Compounds; D013861:Thiocyanates; D011193:Potassium Iodide; C081961:hypoiodous acid; C014607:hypothiocyanite ion; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D012974:Sodium Iodide