Project 1 Viral Genomics: surveillance, epidemiology, host response, and viral immunogenicity

Ensuring a world safe from microbial threats remains a pressing challenge. However, significant gaps remain in our understanding of viral diseases. This proposal employs genomics to address these three major needs: Genomic detection and epidemiology of emerging viral threats in humans and vectors<. For emerging viruses, such as Lassa, Ebola, Zika, Powassan, and other NIAID Category A-C Priority Pathogens, the natural prevalence, evolution, genetic diversity, and transmission among and between humans and zoonotic hosts are not well characterized, which threatens our ability to prepare for and even identify human cases when they occur. Pathogen genomics provides critical public health insight into the movement of viral threats. In partnership with established clinical, public health, and academic collaborators in West Africa and Massachusetts, this project will sequence viruses both human patients and zoonotic reservoirs (African rodents, American ticks and mosquitoes), publicly distribute genomic and metagenomic datasets, and rapidly deliver analyses relevant to the evolution, epidemiology and ecology of these viruses, with a focus on insights that may inform the ongoing development work of diagnostics, therapeutics, and other intervention strategies. Tissue-specific and single-cell characterizations of host response and viral dynamics during viral hemorrhagic fever infection<. Viral hemorrhagic fevers (VHFs) like Ebola and Lassa are highly fatal, but how the molecular and cellular host response mechanisms differ between fatal and non-fatal cases is poorly understood. In partnership with NIAID’s Integrated Research Facility in Frederick, MD (BSL-4), this project will sequence â€Â