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http://hdl.handle.net/11375/18121
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DC Field | Value | Language |
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dc.contributor.advisor | James, Mahony | - |
dc.contributor.author | Nelson, Jordan | - |
dc.date.accessioned | 2015-09-24T18:07:39Z | - |
dc.date.available | 2015-09-24T18:07:39Z | - |
dc.date.issued | 2015-11 | - |
dc.identifier.uri | http://hdl.handle.net/11375/18121 | - |
dc.description.abstract | Respiratory syncytial virus (RSV) is a pathogen associated with lower respiratory tract infection, and is a common cause of infant hospitalization worldwide. Despite efforts to create safe and cost-effective RSV therapeutics, there remains no vaccine, and antiviral drugs have been developed with limited success. Among the 11 proteins coded by the negative-sense single-stranded RNA genome of RSV, the phosphoprotein (P) and nucleoprotein (N) aid in the formation of an RNA-dependent RNA polymerase (RdRp) complex, which is essential for RSV virulence. The specificities of the N-P binding interaction have been researched extensively, which has provided researchers with a novel target for an RSV therapeutic. In this study, a recombinant peptide mimetic (P220-241) containing the final 21 C-terminal amino acids of RSV P fused to Maltose-Binding Protein (MBP), and a cell-penetrating peptide (CPP), was purified for the purpose of targeting this interaction. In addition to successfully entering cells, the peptide was shown to inhibit both RSV subtype A and subtype B infection in vitro, with a percent inhibition (PI) of infection as high as 95% at 20 μM. Additionally, P220-241 did not inhibit infection of parainfluenza virus type 2 (PIV-2), indicating this inhibition was not an artifact of the peptide acting as a pathogen-associated molecular pattern (PAMP). A series of three different assays demonstrated that P220-241 does not appear to have any cytotoxic effects in vitro. Finally, using both glutathione S-transferase (GST) pull-downs and in vitro immunoprecipitations, we demonstrated that P220-241 is able to bind the N protein, while also preventing binding of full-length P protein. Taken together, this study provides the framework for a novel method of targeting RSV protein-protein interactions using chimeric cell-penetrating peptide mimetics. | en_US |
dc.language.iso | en | en_US |
dc.subject | Respiratory Syncytial Virus, Phosphoprotein | en_US |
dc.title | Targeting Respiratory Syncytial Virus Using a Chimeric Phosphoprotein Mimetic | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Medical Sciences (Molecular Virology and Immunology Program) | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Nelson_Jordan_C_2015_MSc.pdf | 3.12 MB | Adobe PDF | View/Open |
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