The objective of this proposal is to identify the role of autophagy regulation of innate and adaptive immunity in dengue virus (DENV)-infected cells. Infection with one of the four serotypes of DENV generates long-term homotypic immunity;however, studies have identified an association of preexisting immunity to one DENV serotype with a greater risk of developing more severe disease, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), during subsequent infection with a different DENV serotype. Several studies have also shown DENV strain-related differences in activation of innate immune pathways. Autophagy intersects with both innate and adaptive immune mechanisms. Recent studies have demonstrated DENV-induced activation of autophagy, but have not fully defined its interaction with innate and adaptive immunity and have not considered strain-related factors. This project will investigate the effects of DENV strains with different profiles of induction of type I interferon on autophagy and the effects of infection on innate and adaptive immune responses. This objective will be accomplished through the following Specific Aims: 1. We will investigate the induction of autophagy and signaling through the mitochondrial antiviral signaling (MAVS) pathway in primary human and murine monocytes and dendritic cells infected with different DENV strains. 2. We will investigate the effects of autophagy on dendritic cell activation and expression of co-stimulatory molecules and cytokines induced by different DENV strains and the downstream effects on anfigen presentation and activation of DENV-specific T cells. These studies will elucidate strain-related differences in driving innate and adaptive immune responses that might be targeted as part of immunomodulatory therapies for dengue.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZGM1-TWD-A)
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University of Rhode Island
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McAllaster, Michael R; Sinclair-Davis, Amy N; Hilton, Nicholas A et al. (2016) A unified approach towards Trypanosoma brucei functional genomics using Gibson assembly. Mol Biochem Parasitol 210:13-21
Li, Ming; Tucker, Lynne D; Asara, John M et al. (2016) Stem-loop binding protein is a multifaceted cellular regulator of HIV-1 replication. J Clin Invest 126:3117-29
Li, Ming; Ramratnam, Bharat (2016) Proteomic Characterization of Exosomes from HIV-1-Infected Cells. Methods Mol Biol 1354:311-26
McAllaster, Michael R; Ikeda, Kyojiro N; Lozano-Núñez, Ana et al. (2015) Proteomic identification of novel cytoskeletal proteins associated with TbPLK, an essential regulator of cell morphogenesis in Trypanosoma brucei. Mol Biol Cell 26:3013-29
Arsenault, Amanda B; Bliss, Joseph M (2015) Neonatal Candidiasis: New Insights into an Old Problem at a Unique Host-Pathogen Interface. Curr Fungal Infect Rep 9:246-252
Li, Ming (2015) Proteomics in the investigation of HIV-1 interactions with host proteins. Proteomics Clin Appl 9:221-34
Medin, Carey L; Valois, Sierra; Patkar, Chinmay G et al. (2015) A plasmid-based reporter system for live cell imaging of dengue virus infected cells. J Virol Methods 211:55-62
Nixon, Christian P; Cheves, Tracey A; Sweeney, Joseph D (2015) Sulfamethoxazole-induced thrombocytopenia masquerading as posttransfusion purpura: a case report. Transfusion 55:2738-41