Targeted development of antivirals against influenza A and respiratory syncytial virus Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/kw52jb78w

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  • 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.
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  • description.provenance : Made available in DSpace on 2009-06-26T22:00:27Z (GMT). No. of bitstreams: 1 Final thesis for Chris Lupfer 6-20-2009.pdf: 1675950 bytes, checksum: 528a9f3fb943c0eed86938324eb8337a (MD5)
  • description.provenance : Approved for entry into archive by Laura Wilson(laura.wilson@oregonstate.edu) on 2009-06-26T22:00:26Z (GMT) No. of bitstreams: 1 Final thesis for Chris Lupfer 6-20-2009.pdf: 1675950 bytes, checksum: 528a9f3fb943c0eed86938324eb8337a (MD5)
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2009-06-26T18:05:04Z (GMT) No. of bitstreams: 1 Final thesis for Chris Lupfer 6-20-2009.pdf: 1675950 bytes, checksum: 528a9f3fb943c0eed86938324eb8337a (MD5)
  • description.provenance : Submitted by Christopher Lupfer (lupferc@onid.orst.edu) on 2009-06-21T05:11:43Z No. of bitstreams: 1 Final thesis for Chris Lupfer 6-20-2009.pdf: 1675950 bytes, checksum: 528a9f3fb943c0eed86938324eb8337a (MD5)

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