Area of Research: HIV/AIDS Dr. Silvija Staprans is working to understand the pathogenesis of HIV infection and the dynamics of HIV and SIV (simian immunodeficiency virus) replication in infected humans and nonhuman primates, respectively. Dr. Staprans also runs the Emory CFAR Virology/Pharmacology Core, which serves as a resource for both Emory and non-Emory investigators by performing highly quantitative virologic assays. Dr. Staprans holds joint appointments as Assistant Professor in the departments of Medicine and Microbiology and Immunology in the Emory University School of Medicine. She received her Ph.D. in biology from the University of California, San Diego, where she also did her post-doctoral training. Research Our studies aim to elucidate:
To address these questions, we study several different simian immunodeficiency virus (SIV)-infected monkey models of AIDS. Animal models allow elucidation of complex virus and host dynamics that are not recapitulated in tissue culture, as well as the possibility to test concepts relevant to HIV infection of humans. Our in vivo research includes observational natural history studies, and studies looking at the effects of various interventions on virus replication dynamics. We pay close attention to how well the different SIV infection models recapitulate HIV infection of humans. We are currently developing an improved SIV challenge model that better recapitulates the low virus inoculum associated with human exposures to HIV. This low-dose challenge model should provide a more sensitive, physiologically relevant measure of the efficacy of vaccines, microbicides, and other prevention strategies. Our in vivo studies demonstrate the link between CD4 T cell activation and the replication of the CD4 T cell-tropic HIV and SIV. Virus replication in activated T cells may serve to both spread virus infection, and to destroy T cells, including antigen-specific CD4+ T cells. We are particularly interested in the early host lymphocyte and virus dynamics that determine whether infection results in a pathogenic or protective response to virus. Because the study of virus dynamics requires precise measures of virus replication, a major focus of the laboratory is the ongoing refinement of sensitive nucleic acid-based methods to measure virus replication and viral variation in vivo. For this we use both PCR- and in situ hybridization-based methods to analyze viral replication in a variety of lymphoid tissues. Using combined quantitative immunologic and virologic techniques we investigate the relationship between early T cell responses and virus replication. We alter these early host-virus dynamics through vaccine or other immunomodulatory interventions. These altered dynamics are elucidating the role of specific lymphocyte populations in controlling the level of SIV replication, provide predictors of infection outcome, and may provide objective markers to guide vaccine development. Our recent studies demonstrated that a vaccine that induced a virus-specific memory CD4 response without a CD8 response actually led to enhanced SIV replication by providing more activated CD4 T cell targets for infection. These results imply that AIDS vaccines that elicit primarily CD4 but not CD8 responses may make hosts more susceptible to HIV infection and disease. We also study naturally SIV-infected sooty mangabey monkeys, the natural host reservoir for the human HIV-2 epidemic. SIV-infected mangabeys do not develop AIDS, despite high levels of virus in the peripheral blood. Yet the same virus causes AIDS when transferred to non-natural hosts such as Asian macaques. Transfer of SIV from naturally–infected mangabeys to the new non-natural macaque host has allowed us to investigate how the SIV quasispecies adapts to a new host environment, and has identified host-specific patterns of virus evolution. In order to elucidate the mangabey adaptation that avoids an immunopathogenic response to SIV infection, we are performing immunologic, gene expression, and targeted gene-sequencing studies. Research Team Members Ashley Barry, Res Specialist, Supervisor
|
Bio |
