Age-related pathology associated with H1N1 A/California/07/2009 influenza virus infection

Abstract Influenza virus infection causes a spectrum of diseases ranging from mild upper respiratory tract infection to severe lower respiratory tract infection that can lead to diffuse alveolar damage, interstitial and airspace inflammation, or acute respiratory failure. Mechanisms instructing disease severity are not completely understood but host, viral, and bacterial factors influence disease outcome. With age being one host factor associated with higher risk of severe influenza, we investigated regional pulmonary distribution and severity of pneumonia following 2009 H1N1 influenza virus infection in newly weaned, adult, and aged ferrets to better understand age-dependent susceptibility and pathology. Aged ferrets exhibited greater weight loss and higher rates of mortality than adult ferrets, whereas the majority of newly weaned ferrets did not lose weight but had a lack of weight gain. Newly weaned ferrets exhibited minimal pneumonia, whereas adult and aged ferrets showed a spectrum of pneumonia severity. Influenza virus–induced pneumonia peaked earliest in adult ferrets, whereas aged ferrets had delayed presentation. Bronchial severity differed between groups, but bronchial pathology was comparable among all cohorts. Alveolar infection was strikingly different between groups. Newly weaned ferrets showed little alveolar cell infection. Adult and aged ferrets demonstrated alveolar infection, but aged ferrets were unable to clear infection. These different age-related pneumonia and infection patterns suggest therapeutic strategies to treat influenza should be tailored contingent on age.