Project Summary/Abstract Listed in the WHO top nine most dangerous pathogens, SFTSV has 12-30% fatality rates, rapidly spreads through tick-to-animal/human, human-to-human and animal-to-human and induces immunopathogenic disease with a characteristic thrombocytopenia. Virus reassortment is a process of genetic recombination that is exclusive to segmented RNA viruses in which co-infection of a cell of natural host and vector with multiple viruses may result in the shuffling of gene segments to generate progeny viruses with novel genome combinations. Reassortment greatly affects virus fitness and directly influences antigenic variation, confounding available methods of virus control. In this application, we will test the hypothesis that tick-mediated natural course of SFTSV infection and reassortment introduces phenotypic changes of fitness, transmissibility, antigenicity, or pathogenicity into progeny reassortants. The goal of this study is to demonstrate the natural course of SFTSV infection and reassortment for fitness, immunogenicity, transmissibility, and pathogenesis in in vitro and in vivo animal models and H. longicornis ticks, ultimately bridging basic research to clinical application.