Enhancement of Respiratory Mucosal Antiviral Defenses by the Oxidation of Iodide

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 H2O2-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 airw...