Intrahost evolution of Lassa virus during acute infection and virus persistence

• Applicant: Dr. Sophie Duraffour
• Subject Area: Virology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511260616

Every year, hundreds of thousands of people become infected with Lassa virus (LASV). It is endemic in West Africa, with Nigeria being the most affected country. Transmission to humans occurs primarily through contact with infected rodents of the species Mastomys natalensis. About 80% of infections are asymptomatic. A small proportion of LASV infections lead to an acute viral haemorrhagic disease, Lassa fever, with a case fatality rate of 20%. There are neither effective therapies nor vaccines. Little is known about pathogenesis factors. After recovery from acute illness, the virus persists in various body fluids. We hypothesise that changes in the viral genome during the course of infection play a role in the pathophysiology of acute disease and viral persistence, an aspect that has not yet been explored. Therefore, in this project we aim to elucidate viral evolution within the host and examine a possible role in disease progression and persistence. To do this, we will use a unique collection of patient samples from two longitudinal studies in Nigeria in which Lassa fever patients were followed both during hospitalisation and months to years after discharge. In the latter study, significant viral persistence was found, particularly in semen samples. We will develop experimental protocols for sensitive and detailed description of viral sequences in all sample types. These protocols will then be used to deep-sequencing the virus at different time points in the course of the disease; both in patients who died from the disease and in survivors in whom the virus persisted to varying degrees. Using these data, we aim to reconstruct the dynamics of the genetic diversity of LASV in different body fluids and relate it to factors of acute disease or persistence.

• DFG Programme: Research Grants
• International Connection: Belgium, Nigeria
• Partner Organisation: Fonds Wetenschappelijk Onderzoek - Vlaanderen ; Research Foundation Flanders (FWO)
• Cooperation Partners: Dr. Cyril Oshomah Erameh; Liana Kafetzopoulou, Ph.D.; Professor Philippe Lemey, Ph.D.