archives@tulane.edu / Immune signatures are patterns of gene and protein expression in immune cells that characterize states of activation and response. As such, signatures indicative of viral control during natural infection may guide vaccine development efforts to achieve similar patterns of protection. Here, we used nonhuman primate (NHP) models of Zika virus (ZIKV) and simian immunodeficiency virus (SIV, as a model for HIV) to explore outcomes of infection in these important human pathogens. We employed a multifaceted approach including high dimensional flow cytometry and RNA sequencing to understand cellular responses to ZIKV generally and during pregnancy, as well as to identify the impacts of infection in astrocytes, a neuroglial target of ZIKV thought to be important in the development of neurologic disease. We found that CD8 T cells may restrict ZIKV persistence in tissues but ultimately have a minimal role in protection to either primary or secondary challenge. However, we showed that immune manipulation, either naturally through pregnancy or artificially through depletion experiments, can skew metabolic and innate immune pathways in unexpected ways. While cellular immunity appeared to minimally impact ZIKV infection, such responses in SIV are important in controlling viral replication, which we inversely showed by tracking patterns of viral mutation to evade CD8 responses. We also identified transcriptional signatures in ZIKV infection that may underlie the development of neurologic diseases and found that different virus lineages have unique impacts on gene expression. Together, these experiments showcase the utility of profiling approaches in understanding the immune complexity that accompanies viral infection. / 1 / Blake Schouest
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_119697 |
| Date | January 2020 |
| Contributors | Schouest, Blake (author), Maness, Nicholas (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 141 |
| Rights | 12 months, Copyright is in accordance with U.S. Copyright law. |
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