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Spatial and temporal EVOlution of LASSa virus in West Africa

Subject Area Virology
General Genetics and Functional Genome Biology
Term from 2021 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 458954254
 
Final Report Year 2025

Final Report Abstract

Lassa fever is a rodent-borne zoonotic ailment that kills thousands of people every year in Western Africa. The causative Lassa virus (LASV) is hosted mainly by the Natal multimammate mouse Mastomys natalensis, and also other rodent species. Humans become infected when exposed to rodent droppings. Genetic sequences represent key data for assessing LASV evolution and molecular epidemiology. Unfortunately, the availability of whole LASV genomes in public databases such as GenBank is lopsided, with 450 full sequences obtained from humans compared to only 28 acquired from rodents. Generating whole LASV genomes from virus-positive rodent samples collected during 2003- 2019 within Guinea and Nigeria, West Africa, our objectives were: 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. Biosafety-4 inactivation and extraction of LASV-positive samples for RNA were carried out at the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (BNITM). Extracts were shipped to the Dresden-Concept Genome Centre and sequence assembly carried out in collaboration with the Centre for Virus Research, University of Glasgow, United Kingdom. 155 out of 342 realizable LASV genomes (45%) were sequenced at 98-100 % coverage. 120/342 (35%) other genomes were sequenced to varying levels of coverage below 98 %. Our analyses so far have enabled us to publish two initial scientific articles. In remaining LASSEVO analyses, we will re-extract relevant samples and reassemble subpar genomes to increase our high-coverage collection beyond 155. The expanded rodent-derived dataset will be analysed in order to provide further insight into the evolution, genome shifting and molecular epidemiology of LASV. Challenges we faced during this project include the intricacies in retrieving our LASV-positive biopsies from the biosafety 4-lab, and also degradation and bacterial contamination of some of our samples. Additionally, successfully optimising our next generation sequencing workflow with the Dresden-concept genome centre took several months.

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