Intra-host evolution of Lassa virus during acute infection and virus 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 virus 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 intrahost evolution in LASV 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 unravel the intrahost evolutionary dynamics including the role of immune escape in LASV infections.