Spatial and temporal EVOlution of LASSa virus in West Africa

• Applicant: Dr. Elisabeth Fichet-Calvet
• Subject Area: Virology ; General Genetics and Functional Genome Biology
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458954254

Lassa fever is a deadly zoonotic disease that causes thousands of deaths across West Africa annually. The virus that causes this illness (LASV) is borne by rodents, principally the Natal multimammate mouse Mastomys natalensis. Other rodent species such as the Guinea multimammate mouse M. erythroleucus, the African Woodmouse Hylomyscus pamfi and the Pygmy mouse Mus baoulei have also been implicated as natural hosts. Humans become infected when they encounter excreta and the body fluids of these rodents. Genetic sequences represent key data for assessing LASV evolution. Phylogenetic comparison of these sequences can help track who-infected-who during epidemics, providing information that can guide epidemiological interventions. Spatiotemporal analysis of these sequences could also enable health authorities to anticipate how the virus might emerge in new ways geographically and over time. Sequencing the full genome (as opposed to partial fragments) of pathogens like LASV allows for analysis of increased phylogenetic data, and produces more robust, reliable results. Unfortunately, the availability of LASV whole genomes in public databases such as GenBank is lopsided, with 450 full sequences obtained from humans compared to only 28 acquired from rodents. In addition, interpretations of LASV phylogeography and epidemiology based on these human-derived genomes may have been distorted by the perpetual tendency of humans for long-distance travel, introducing the possibility that their sites of detection and actual infection are disparate. Conversely, we expect similar analyses on rodents (which on their own rarely exceed their small home ranges) to yield a more realistic picture of LASV spread and transmission. This project focuses on whole genome sequencing of LASV from 399 virus-positive rodent blood samples collected during 2003-2019 within Guinea and Nigeria, West Africa. The samples are currently gathered in cold storage at the Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany. Phylogenetic analysis of these full genomes will enable us attain the following objectives: 1) to investigate LASV evolution in the rodent Mastomys natalensis in highly endemic areas for Lassa fever, 2) to investigate the LASV genome shifting under a selective pressure, 3) to study the molecular epidemiology of LASV, and 4) to compare the LASV genome obtained in rodents to those obtained in humans. We believe our results will contribute significantly to insight concerning LASV change and dispersal in its natural reservoir. This knowledge is vital to more intelligent prevention and control of Lassa fever within West Africa.

• DFG Programme: Research Grants
• International Connection: Nigeria
• International Co-Applicant: Ayodeji Opeyemi Adewole Olayemi, Ph.D.