Graduate Thesis Or Dissertation
 

Targeted development of antivirals against influenza A and respiratory syncytial virus

Public Deposited

Downloadable Content

Download PDF
https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/kw52jb78w

Descriptions

Attribute NameValues
Creator
Abstract
  • Influenza A and Respiratory Syncytial Virus (RSV) are both enveloped, negative strand RNA viruses which infect the respiratory mucosa of animals and humans. Despite decades of research and development of antivirals and vaccines, both of these viruses continue to be a major health concern throughout the world. The focus of my research was to examine alternative ways of developing antiviral which would be both faster and more effective than conventional methods of screening libraries of compounds. By examining the nucleotide sequences of influenza A virus my colleagues and I were able to determine conserved regions as candidates for antisense drug targets. Lead antisense compounds were effective at inhibiting influenza A virus replication in a Balb/C mouse model. Although resistance was observed in some strains, a combination of antisense targeting multiple conserved regions was effective. One limitation of the antisense used in these experiments was their inability to inhibit virus replication when administered more than 2h after infection. For RSV, I examined the potential of targeting a cellular protein (ubiquitin) thought to interact with and be required for RSV replication. I utilized currently available drugs to interfere with ubiquitin recycling through the proteasome. Treatment with proteasome inhibitors reduced virus replication in cell culture and had an indirect effect on RSV virion formation. However, treatment of RSV infection with a proteasome inhibitor in a Balb/C mouse model resulted in an altered immune response, increased pathology in the lungs, and increased mortality. From these results I conclude that unless sufficient background information is available for the target of interest, the targeted development of antivirals for influenza A and RSV is no more effective than conventional methods.
License
Resource Type
Date Available
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Subject
Rights Statement
Publisher
Peer Reviewed
Language
Replaces

Relationships

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details Final_thesis_for_Chris_Lupfer_6-20-2009.pdf 2017-08-08 Public Download