Reverse genetics systems as tools to overcome the genetic diversity of Lassa virus

Lassa virus is endemic in a large area of sub-Saharan Africa, and exhibits a large amount of genetic diversity. Of the four currently recognized lineages, lineages I–III circulate in Nigeria, and lineage IV circulates in Sierra Leone, Guinea, and Liberia. However, several newly detected lineages have been proposed. LASV genetic diversity may result in differences in pathogenicity or response to medical countermeasures, necessitating the testing of multiple lineages during the development of countermeasures and diagnostics. Logistical and biosafety concerns can make it difficult to obtain representative collections of divergent LASV clades for comparison studies. For example, lack of a cold chain in remote areas, or shipping restrictions on live viruses can prevent the dissemination of natural virus isolates to researchers. Reverse genetics systems that have been developed for LASV can facilitate acquisition of hard-to-obtain LASV strains and enable comprehensive development of medical countermeasures.