Proteomic analysis reveals down-regulation of surfactant protein B in murine type II pneumocytes infected with influenza A virus

• Published in: Virology (New York, N.Y.) Vol. 483; no. C; pp. 96 - 107
• Main Authors: Kebaabetswe, Lemme P, Haick, Anoria K, Gritsenko, Marina A, Fillmore, Thomas L, Chu, Rosalie K, Purvine, Samuel O, Webb-Robertson, Bobbie-Jo, Matzke, Melissa M, Smith, Richard D, Waters, Katrina M, Metz, Thomas O, Miura, Tanya A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015; Elsevier
• Subjects: Alveolar Epithelial Cells - metabolism; Alveolar Epithelial Cells - virology; Animals; Cells, Cultured; Chromatography, Liquid; Down-Regulation; Fluorescent Antibody Technique; Gene Expression Profiling; Immunoblotting; Infectious Disease; Influenza A virus; Influenza A virus - growth & development; Mass Spectrometry; Mice, Inbred C57BL; Primary alveolar type II epithelial cells; Proteomics; Pulmonary Surfactant-Associated Protein B - metabolism; Quantitative proteomics; Surfactant protein B; Surfactant protein B; Primary alveolar type II epithelial cells; Quantitative proteomics; Influenza A virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.03.045

Abstract Infection of type II alveolar epithelial (ATII) cells by influenza A viruses (IAV) correlates with severe respiratory disease in humans and mice. To understand pathogenic mechanisms during IAV infection of ATII cells, murine ATII cells were cultured to maintain a differentiated phenotype, infected with IAV-PR8, which causes severe lung pathology in mice, and proteomics analyses were performed using liquid chromatography–mass spectrometry. PR8 infection increased levels of proteins involved in interferon signaling, antigen presentation, and cytoskeleton regulation. Proteins involved in mitochondrial membrane permeability, energy metabolism, and chromatin formation had reduced levels in PR8-infected cells. Phenotypic markers of ATII cells in vivo were identified, confirming the differentiation status of the cultures. Surfactant protein B had decreased levels in PR8-infected cells, which was confirmed by immunoblotting and immunofluorescence assays. Analysis of ATII cell protein profiles will elucidate cellular processes in IAV pathogenesis, which may provide insight into potential therapies to modulate disease severity.