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Evolution of the Virulent Primary Isolate, SIV/DeltaB670, in vivo,Implications for Study Design and Antiviral Therapies

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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Taber, Rachelratst21@pitt.eduRATST21
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMurphey-Corb, Michael
Committee MemberThomson, Angus W
Committee MemberFlynn, JoAnne L
Committee MemberDeLuca, Neal A
Committee MemberBarratt-Boyes, Simon M
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:, etd-12132006-182005
Date Deposited: 10 Nov 2011 20:10
Last Modified: 15 Nov 2016 13:54


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