dc.creator | Hastings, Andrew Kenneth | |
dc.date.accessioned | 2020-08-21T21:12:34Z | |
dc.date.available | 2015-03-26 | |
dc.date.issued | 2015-03-26 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03172015-144524 | |
dc.identifier.uri | http://hdl.handle.net/1803/10838 | |
dc.description.abstract | My thesis project explores mechanisms of innate immune evasion by human metapneumovirus (HMPV), as well as the consequences of a lack of type I IFN (IFNAR) signaling on host response and pathogenesis. I show that the expression of the small hydrophobic (SH) of HMPV inhibits type I IFN signaling through targeting signal transducers and activators of transcription 1 (STAT1). Next, I demonstrate that IFNAR signaling is important for the early control of HMPV replication and the development of functional CD8+ T cell (TCD8) response, but it also makes a significant contribution to disease pathogenesis. The effect on a functional T cell response depends on signaling in the bone-marrow compartment, while signaling on the lung epithelium drives pathogenesis. Additionally, the development of decreased functionality in IFNAR-/- mice correlates with expression of the inhibitory T cell receptor T cell immunoglobulin mucin-3 (TIM-3), and a greater ratio of alveolar macrophages to dendritic cells (DCs) early in infection. Taken together, I have revealed mechanisms by which HMPV is capable of evading type I IFN, and I have further elucidated the implications of IFNAR signaling evasion on the TCD8 response. | |
dc.format.mimetype | application/pdf | |
dc.subject | STAT1 | |
dc.subject | virus | |
dc.subject | human metapneumovirus | |
dc.subject | HMPV | |
dc.subject | typ I IFN | |
dc.subject | IFN | |
dc.subject | innate immunity | |
dc.subject | jak/stat | |
dc.subject | virus | |
dc.subject | IFN | |
dc.subject | interferon | |
dc.subject | T cell | |
dc.subject | inhibitory T cell pathways | |
dc.title | Evasion of type I IFN signaling by the small hydrophobic protein of HMPV and the implications for viral replication and pathogenesis | |
dc.type | dissertation | |
dc.contributor.committeeMember | Sebastian Joyce | |
dc.contributor.committeeMember | Mark Denison | |
dc.contributor.committeeMember | R. Stokes Peebles | |
dc.contributor.committeeMember | John V. Williams | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-03-26 | |
local.embargo.lift | 2015-03-26 | |
dc.contributor.committeeChair | Louise Rollins-Smith | |