Evolution of the Virulent Primary Isolate, SIV/DeltaB670, in vivo, Implications for Study Design and Antiviral Therapies
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.
Advisor:Michael Murphey-Corb, Ph.D.; Neal A. DeLuca, Ph.D.; Angus W. Thomson, Ph.D., D.Sc.; Simon M. Barratt-Boyes, D.V.M, Ph.D.; JoAnne L. Flynn
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Keywords:molecular virology and microbiology
Date of Publication:01/05/2007