Taber, Rachel
(2007)
Evolution of the Virulent Primary Isolate, SIV/DeltaB670, in vivo,Implications for Study Design and Antiviral Therapies.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Antiretroviral drug treatments and vaccine strategies are hampered by the ability of the HIV to generate variants able to evade their protective effects. Understanding the effects of these interventions on virus evolution could aid in the design of targeted antiviral strategies. We addressed this in a cohort of SIV infected non-human primates given short-term antiviral drug treatment (ART) with and without DNA vaccinations. We hypothesized that the most potent therapies (e.g. those that suppress virus burden to the greatest degree) would limit virus evolution. Our results supported this hypothesis. There was no apparent vaccine effect however. These results could indicate that the immune response was not strong enough to induce changes in the global virus population, evolution must be monitored at the epitope level to be revealed, or the most informative time points were unavailable due to low virus burdens. We additionally hypothesized that infection of the gut associated lymphoid tissue may render this organ as a reservoir for expression of unique viral genotypes. We demonstrated that high plasma virus loads were associated with high tissue virus loads and wide dissemination of genotypes. In contrast, the lymphoid tissues on animlals that controlled their virus burden contained genotypes not expressed in other organs. Our results have important implications on studying virus evolution in vivo by demonstrating that large populations and potentially numerous virus genes need to be analyzed.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Murphey-Corb, Michael | | | | | Committee Member | Thomson, Angus W | | | | | Committee Member | Flynn, JoAnne L | | | | | Committee Member | DeLuca, Neal A | | | | | Committee Member | Barratt-Boyes, Simon M | | | |
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| Date: |
5 January 2007 |
| Date Type: |
Completion |
| Defense Date: |
14 December 2006 |
| Approval Date: |
5 January 2007 |
| Submission Date: |
13 December 2006 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
GALT; heteroduplex tracking analysis; monotherapy; mucosa; PMPA |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-12132006-182005/, etd-12132006-182005 |
| Date Deposited: |
10 Nov 2011 20:10 |
| Last Modified: |
15 Nov 2016 13:54 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10360 |
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