Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus

William Domm, Min Yee, Ravi S. Misra, Robert Gelein, Aitor Nogales, Luis Martinez-Sobrido, Michael A. O'Reilly
2017 American Journal of Physiology - Lung cellular and Molecular Physiology  
Domm W, Yee M, Misra RS, Gelein R, Nogales A, Martinez-Sobrido L, O'Reilly MA. Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus. Infants born prematurely often require supplemental oxygen, which contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV)
more » ... ction. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with IAV [IAV (A/Hong Kong/X31) H3N2] as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescence-expressing reporter strain of H1N1 IAV [A/Puerto Rico/ 8/34 mCherry (PR8-mCherry)] to evaluate whether it also altered early infection of the respiratory epithelium. Like Hong Kong/X31, neonatal hyperoxia increased morbidity and mortality of adult mice infected with PR8-mCherry. Whole lung imaging and histology suggested a modest increase in mCherry expression in adult mice exposed to neonatal hyperoxia compared with room air-exposed animals. However, this did not reflect an increase in airway or alveolar epithelial infection when mCherry-positive cells were identified and quantified by flow cytometry. Instead, a modest increase in the number of CD45-positive macrophages expressing mCherry was detected. While neonatal hyperoxia does not alter early epithelial infection with IAV, it may increase the activity of macrophages toward infected cells, thereby enhancing early epithelial injury. epithelial cells; influenza A virus infection; neonatal oxygen; hyperoxia; reporter-expressing influenza A virus; single-cycle infectious influenza A virus
doi:10.1152/ajplung.00203.2017 pmid:28798254 fatcat:cyeb5jnuyjh5zeccvkz3xppfda