Support for Emerging Virus and Arbovirus Research - ABSTRACT As underscored by West Nile, Zika, dengue, yellow fever and chikungunya viruses, new and emerging zoonotic viruses and arboviruses represent increasing threats to human health, yet their mechanisms of emergence remain poorly understood, and effective interventions are largely lacking. Research on their pathogenesis, ecology, evolution, epidemiology, emergence mechanisms, diagnostics, vaccines and therapeutics remain critical public health and national security needs. The Reference Center at UTMB comprises a comprehensive collection of over 9,000 virus strains in 21 families, spanning a broad temporal and geographic distribution of most, as well as associated antisera, antigens, cDNA clones, and other reagents to enable research. Hundreds of new virus strains are added and hundreds of viruses and reagents are shipped annually, and new strains are actively acquired through investigator deposits and novel isolations. Unlike other repositories, the Reference Center also maintains broad expertise in both novel and traditional approaches to virus identification and characterization, as well as for studies of evolution, epidemiology, ecology, pathogenesis, and countermeasure development. We also provide critical support for emergency responses by rapidly generating and distributing critical reagents prioritized by many scientific and public health institutions. Furthermore, through the training of domestic and international scientists, new relationships are established that enhance our collections, improve early stages of outbreak detection and control in endemic regions, and thereby enhance biosecurity in the U.S. and worldwide. This proposal seeks to support Reference Center activities through four Specific Aims: 1. Maintain a comprehensive set of emerging viruses, arboviruses and reagents to support research and surveillance. Our vast collection of viruses, antigens, antibodies, cDNA clones, animal models and reagents will be continually expanded and enhanced to address emergences and capitalize on new technologies. 2. Discover, isolate and characterize new viruses to determine relationships and taxonomic assignments, and to assess in vitro and in vivo host range. Clinical and field samples as well as viral isolates will be received for identification and characterization, and added to the repository. Critical phenotypes of new viruses and strains will be assessed by using in vitro and in vivo infections and other approaches. 3. Perform sequencing, phylogenetic analyses and reverse genetics of selected virus groups to determine evolutionary histories and emergence mechanisms, patterns of spread/infection, and to rapidly determine the sources of new outbreaks. Key virus strains will undergo genomic sequencing to generate databases that can be exploited for outbreak response and pandemic preparedness. 4. Train scientists in the identification and characterization of emerging viruses. Capacity strengthening through training of visiting scientists will enhance research and surveillance in the U.S. and worldwide to rapidly diagnose new outbreaks and limit their spread from endemic/enzootic locations.
