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Published on: January 12, 2024
Quantitative proteome profiling of respiratory virus-infected lung epithelial cells
Angela van Diepen1, H Kim Brand, Iziah Sama
1Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Abstract:
Respiratory virus infections are among the primary causes of morbidity and mortality in humans. Influenza virus, respiratory syncytial virus (RSV), parainfluenza (PIV) and human metapneumovirus (hMPV) are major causes of respiratory illness in humans. Especially young children and the elderly are susceptible to infections with these viruses. In this study we aim to gain detailed insight into the molecular pathogenesis of respiratory virus infections by studying the protein expression profiles of infected lung epithelial cells. A549 cells were exposed to a set of respiratory viruses [RSV, hMPV, PIV and Measles virus (MV)] using both live and UV-inactivated virus preparations. Cells were harvested at different time points after infection and processed for proteomics analysis by 2-dimensional difference gel electrophoresis. Samples derived from infected cells were compared to mock-infected cells to identify proteins that are differentially expressed due to infection. We show that RSV, hMPV, PIV3, and MV induced similar core host responses and that mainly proteins involved in defense against ER stress and apoptosis were affected which points towards an induction of apoptosis upon infection. By 2-D DIGE analyses we have gathered information on the induction of apoptosis by respiratory viruses in A549 cells.
Insights
Respiratory viruses like RSV and hMPV trigger similar host responses, primarily affecting proteins involved in ER stress and apoptosis. This suggests viral infections induce programmed cell death in lung epithelial cells.
Area of Science:
- * Molecular biology
- * Virology
- * Cellular biology
Background:
- * Respiratory virus infections are a leading cause of human illness and death.
- * Viruses such as respiratory syncytial virus (RSV), parainfluenza (PIV), and human metapneumovirus (hMPV) are significant contributors to respiratory diseases, particularly in vulnerable populations like young children and the elderly.
Purpose of the Study:
- * To investigate the molecular pathogenesis of respiratory virus infections.
- * To analyze protein expression profiles in infected lung epithelial cells to understand host responses.
Main Methods:
- * A549 lung epithelial cells were infected with RSV, hMPV, PIV3, and Measles virus (MV) using live and UV-inactivated preparations.
- * Proteomics analysis was performed using 2-dimensional difference gel electrophoresis (2-D DIGE) at various time points post-infection.
- * Differential protein expression was identified by comparing infected cells to mock-infected controls.
Main Results:
- * RSV, hMPV, PIV3, and MV induced comparable core host responses.
- * Proteins primarily affected were those involved in defense against endoplasmic reticulum (ER) stress and apoptosis.
- * The observed changes indicate an induction of apoptosis in lung epithelial cells following infection.
Conclusions:
- * Respiratory virus infections trigger a conserved host response involving ER stress and apoptosis pathways.
- * 2-D DIGE analysis provides insights into the induction of apoptosis by various respiratory viruses in A549 cells.
- * Understanding these molecular mechanisms is crucial for developing effective treatments against respiratory viral diseases.
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