The evolutionary genomics of Lassa Virus virulence and persistence

Lassa virus (LASV) is an endemic virus in West Africa that infects hundreds of thousands of individuals each year. Humans primarily become infected through contact with rodents of the genus Mastomys that shed viruses in their urine and faeces. About 80% of people who become infected remain asymptomatic, but 1 in 5 LASV infections result in an acute viral haemorrhagic illness. No effective treatments or vaccines exist and little is known about the determinants of disease development. In addition, it remains unclear to what extent LASV may persist in survivors. In this project, we aim to disentangle the role of the viral genotype as well as intrahost evolution in disease outcome and persistence. In collaboration with the Bernhard-Nocht Institute for Tropical Medicine, we will leverage the comprehensive sampling from two ongoing studies in Nigeria that monitor patients in a hospital ward as well as long-term upon discharge. The latter identified a considerable degree of persistence, in particular in semen sampling. We will generate whole-genome deep sequencing data from multiple time points from patients that succumb to infection and patients that survive with varying degrees of persistence. Using this data, we will study the intrahost evolutionary dynamics including the role of immune escape in LASV infections. Finally, we will perform a large-scale phylogenomics study to determine to what extent the viral genotype determines virulence and elucidate its molecular determinants.