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Abstract

Influenza viruses, major agents of respiratory diseases, are responsible for epidemics resulting in high mortality and morbidity every year. A better understanding of virus-host interactions on a cellular level may help to explain the different mechanism of virulence and pathogenesis and to control future outbreaks. Furthermore, knowledge on specific virus-host interactions relevant for cell culture-based influenza vaccine production processes might help to optimize virus yields and antigen quality in upstream processing. The aim of this study was to characterize host cell protein expression changes in canine MDCK and human A549 cells after infection with human influenza A/PR/8/34 (H1N1). Host cell proteins from different infection phases were studied by two-dimensional differential gel electrophoresis (2D-DIGE). Differences in relative protein expression were quantified in order to obtain a time-dependent proteomic coverage of host cell response. Differentially expressed proteins, with at least 2.5-fold expression changes and p values of 0.001 or less, were identified by mass spectrometry (LC-MS/MS). Here, we present proteins identified with these criteria. They are reported to be involved in a wide spectrum of cellular functions and host defense mechanisms including, especially: apoptosis, cytoskeletal rearrangement or protein synthesis and degradation. Distinct proteome patterns with differentially regulated proteins over time showed dynamic host cell response mechanisms in early and late phase of infection. Notably, our data indicate that influenza A virus induces different host defense mechanisms comparing human and canine cells. Surprisingly, significant differences in host cell response were observed comparing results from the same virus strain (H1N1) from different suppliers (RKI, Germany; NIBSC, UK).