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Am J Pathol. 2019 Oct 1. pii: S0002-9440(19)30749-7. doi: 10.1016/j.ajpath.2019.08.017. [Epub ahead of print] Age-related pathology associated with H1N1 A/California/07/2009 influenza virus infection.
Bissel SJ1, Carter CE2, Wang G3, Johnson SK2, Lashua LP4, Kelvin A5, Wiley CA3, Ghedin E6, Ross TM7.
Author information
1 Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: sbissel@iu.edu. 2 Center for Vaccines and Immunology. 3 Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. 4 Center for Genomics & Systems Biology, Department of Biology, College of Arts & Sciences, New York University, New York, NY, USA. 5 Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada; Canadian Centre for Vaccinology, Department of Pediatrics, IWK Health Centre, Halifax, Canada. 6 Center for Genomics & Systems Biology, Department of Biology, College of Arts & Sciences, New York University, New York, NY, USA; Department of Epidemiology, College of Global Public Health, New York University, New York, NY, USA. 7 Center for Vaccines and Immunology,; Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
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.
Copyright ? 2019. Published by Elsevier Inc.
PMID: 31585069 DOI: 10.1016/j.ajpath.2019.08.017