Project description:We profile the peripheral blood of patients infected with West Nile Virus with divergent disease-trajectories (West Nile Encephalitis, West Nile Fever, and asymptomatic) during relatively acute infection and at a convalescent timepoint (~90-days later) using single-cell RNA sequencing in an effort to uncover determinants of disease progression and flesh out the landscape of infection. In the blood of the infected patients, stratified cell-states involved in acute viral infection resolve into more homogenous states at the follow-up blood draws, A dramatic shared transcriptional shift between the primary blood-draws during acute infection and the 90-day follow-ups in all observed compartments allows us to highlight multiple cell-type and cell-state-specific patterns of gene expression.
Project description:Purpose of this experiment was to further understand how innate immune defenses impact host response and West Nile virus tissue tropism. This study examined host-transcriptional response to West Nile virus in permissive and nonpermissive tissues using wildtype mice and mice with genetically altered interferon signaling pathways.
Project description:High throughput sequencing was performed using Illumina HiSeq to identify differentially regulated genes in Culex mosquitoes after West Nile virus infection.
Project description:Individual variations in immune status and function determine responses to infection and contribute to disease severity and outcome. Patients exhibit considerable variation in clinical responses to infection with West Nile virus. We have undertaken a comprehensive characterization of the immune responses of a stratified cohort of patients with a history of West Nile virus infection to identify key mechanisms of resistance and susceptibility. We provide molecular profiles of cellular mechanisms of primary human immune cells defined through multifaceted interrogation including multiplexed gene expression analysis integrated with highly sensitive multidimensional flow cytometry. The availability of reliably curated patient cohorts and data-sharing and data mining techniques of high-throughout investigations should accelerate identification of critical elements of immune resistance to important pathogens
