UCSF

The first three chapters of this dissertation explore the pathogenesis of viruses infecting the human developing brain. Specifically, the tropism and consequences of infection by Zika and rubella virus are defined. While Zika virus was found to infect primarily radial glia and astrocytes, and rubella appeared to target microglia, both stimulate a strong response consistent with type I interferon signaling. The next chapter addresses a rare disease that likewise stems from overactivation of immune response, in this case, inflammation of the vessels of the brain. An exploration of abnormal molecular pathways in primary angiitis of the central nervous system revealed dysregulation of the complement system. Chapters five through eight investigate infectious diseases and commensal microbiota of wildlife. These include epizootics among sharks and parrots, and a demonstration of how metagenomic next-generation sequencing can color in an ecological diagram of mosquitoes, their bloodmeal hosts, and the commensals and pathogens they carry. Diving deeper into one component of the mosquito microbiota, the final chapters grapple with a surprising feature of the narnavirus genome. These simple entities, named NAked-RNA-viruses, turn out to be far more complex than previously recognized.