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Dissertation
Molecular changes in alveolar epithelial cells during influenza virus infection
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2018
DOI:
https://doi.org/10.17918/m11w-0c47
Abstract
Annual influenza virus infection represents a concern for public health and a financial burden as it results in approximately 500,000 deaths and 5,000,000 hospitalizations as reported by the World Health Organization (WHO). Influenza virus infection begins with the attachment and entry of alveolar epithelial cells within the respiratory tract of susceptible hosts. During infection, influenza virus hijacks the cellular machinery in order to replicate its genome and produce new progeny virions to spread the infection. As not all alveolar epithelial cells are infected during influenza virus replication, we queried what the transcriptomic differences were between directly infected epithelial cells compared to bystander uninfected epithelial cells isolated from mice at day three post infection with a green fluorescent protein expressing A/Puerto Rico/8/1934 influenza virus. Using RNA sequencing, we identified the downregulation of Wnt signaling during influenza virus infection and our studies suggest that this might be a host response to initiate repair mechanisms necessary to restore lung function. We have also identified a novel transcript, Heatr9 that we found to be upregulated following influenza virus infection and whose expression plays a role in chemokine ligand induction and release. Beyond differences in protein coding genes, we also show that the long noncoding RNA profile of influenza virus infected epithelial cells is unique and that Zfas1, a long noncoding RNA found to be induced following influenza virus infection, plays a role in preventing apoptosis, a mechanism that may benefit viral replication in vivo in the highly inflammatory environment of the lung. These studies demonstrate the novel effects of direct influenza virus infection compared to mere exposure to an inflammatory environment and offer a platform for future studies to explore the specific pathways and interactions between influenza virus and host cells.
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Details
- Title
- Molecular changes in alveolar epithelial cells during influenza virus infection
- Creators
- Christopher James Stairiker - DU
- Contributors
- James M. Burns Jr. (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 200 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 8232; 991014632715204721