%0 Journal Article %T A novel BSL-2 Lassa virus reverse genetics system modelling the complete viral life cycle. %A Hu X %A Bai X %A Tian F %A Xing Y %A Shi Y %A Tong Y %A Zhong J %J Emerg Microbes Infect %V 13 %N 1 %D 2024 Dec 15 %M 38747061 %F 19.568 %R 10.1080/22221751.2024.2356149 %X 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.