{Reference Type}: Journal Article {Title}: A novel BSL-2 Lassa virus reverse genetics system modelling the complete viral life cycle. {Author}: Hu X;Bai X;Tian F;Xing Y;Shi Y;Tong Y;Zhong J; {Journal}: Emerg Microbes Infect {Volume}: 13 {Issue}: 1 {Year}: 2024 Dec 15 {Factor}: 19.568 {DOI}: 10.1080/22221751.2024.2356149 {Abstract}: Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.