Lassa virus: unravelling the within-host evolutionary dynamics of acute and persistent infections and the virulence evolution among hosts

Lassa fever is an acute viral haemorrhagic illness caused by Lassa virus (LASV) and one of the priority diseases listed by the World Health Organization. The high incidence in Nigeria with an annual rise of 200-300 cases since 2017 and a case fatality rate of 20% highlight the urgent need to intensify LASV research. To this end, two major longitudinal studies in acute and surviving Lassa fever individuals were initiated in Nigeria in 2018 creating a unique dataset of longitudinal samples from more than 150 participants. While these studies set the basis for an improved understanding of LASV viremia and persistence, the extent to which these factors are impacted by intra-host virus evolution remains unaddressed. In this study we will focus on this knowledge gap and use Next Generation Sequencing to generate LASV genomic data from longitudinal samples in conjunction with in-depth evolutionary analysis to elucidate LASV evolution in blood during acute infection and in bodily fluids post-discharge. Additionally, innovative phylogenetic analysis methodology will be used to investigate viral genomic determinants of disease severity, outcome and viral persistence. This will be the first comprehensive analysis of intra-host LASV variation and the first phylogenomic analysis to determine viral genetic factors associated with disease presentation, treatment impact and persistence. Overall, this project will broaden our understanding of LASV infection, outcome and evolutionary dynamics.