Project 4: Genetic drivers of infection by the RNA virus Lassa Virus and implications for human disease

PROJECT 4 PROJECT SUMMARY Lassa virus—the etiological agent of Lassa Fever, a severe hemorrhagic fever with high mortality rates—is an RNA virus endemic to a large region of West Africa. Lassa virus (LASV) is genetically diverse, and current viral lineages circulating in Nigeria and the Mano River Union are estimated to have diverged from each other over 1000 years ago. Viral genetic diversity is suspected to play a role in variability in disease severity observed in some clinical and animal studies. However, to what extent viral genetics plays a role in this phenotype and which loci are most important for disease outcomes remains unknown. To shed light on the role of viral genetic variation on LASV infection and disease, this project will i) interrogate genome-wide inter-lineage variability in infection and replication, and ii) systematically map the impact on viral entry of all variable sites in the LASV glycoprotein, the key gene involved in viral entry, and determine their likely impact on RNA structure and association with sequence conservation. The results of this study will provide novel insights into LASV functional genomics and offer indications for future clinical studies to rigorously investigate variability in disease outcome.