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Dissertation
Influenza A virus infection of the CNS
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2020
DOI:
https://doi.org/10.17918/00000320
Abstract
Influenza A virus (IAV) is primarily known as a respiratory pathogen, infecting lung epithelial cells. Far less is understood about IAV infection of other cell types, especially those of the central nervous system (CNS), despite the ability of multiple neurotropic IAV strains to cause severe, even life-threatening neurological consequences, including encephalitis and meningitis. Research aimed at uncovering the mechanisms by which IAV replicates and spreads within the CNS and how the host responds to infection is therefore of increasing importance. In this dissertation, it was demonstrated that astrocyte derived type I interferon (IFN) is critical to limiting viral replication in neurons. The type I IFN response limited viral loads in mouse brains and prevented viral dissemination out of the CNS. The IFN stimulated gene, Z-DNA binding protein 1 (ZBP1), was found to aid in mouse survival following IAV CNS infection. Even though type I IFN induced ZBP1 in neurons, no anti-viral role for ZBP1 was observed in neurons. Instead, ZBP1 was protective in an anti-inflammatory, astrocytic cell death-dependent manner. Additionally, I showed that a non-neurovirulent strain of the flu is able to infect neurons and elicit high levels of an immune response within the mouse brain following intracerebral infection. While the neurovirulent IAV strain resulted in both neuronal and mouse death, the non-neurovirulent strain did not appear to cause any disease in vitro or in vivo. Lastly, I determined that RNA from the neurovirulent IAV strain is able to be detected in mouse brains months after infection. These studies establish a basic science foundation for which future studies will be aimed at developing therapeutic approaches to limit the neuropathogenesis caused by IAV CNS infection.
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Details
- Title
- Influenza A virus infection of the CNS
- Creators
- Riley Michele Williams
- Contributors
- Glenn Rall (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, 151 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991014856045704721