Researchers from Dr. ZHONG Jin’s group at the Shanghai Institute of Immunity and Infection of the Chinese Academy of Sciences reported a novel biosafety level 2 (BSL-2) Lassa virus (LASV) reverse genetics system. This study was published online in Emerging Microbes & Infections. 

LASV infects human, causing Lassa fever (LF) which is an acute febrile illness characterized by hemorrhage and multisystem damage.  

Currently, there is no approved vaccine and specific antiviral drug against LASV. Due to the high pathogenicity and the lack of effective preventive or treatment measures, LASV is classified as a risk group 4 pathogen, necessitating handling the live virus under biosafety level 4 (BSL-4) conditions. 

In this study, researchers established a helper cell line expressing all LASV viral proteins, which allows for the production of the genome-deficient LASV particles by reverse genetics.  

These deficient LASV particles contain a viral genome that lacks all viral protein-encoding genes, and only harbors critical viral cis-acting elements essential for viral replication, transcription and genome packaging, thus they are non-infectious in natural conditions. On the other hand, the morphology and viral protein composition of these deficient LASV particles resemble those of authentic LASV virions.  

Therefore, this new reverse genetics system could be utilized to infect and propagate in the helper cell line, modeling the complete LASV life cycle safely and effectively in a BSL-2 laboratory. 

By utilizing this system, researchers confirmed that host cellular protein LAMP1 is a crucial intracellular receptor for LASV entry, and found that a previously reported extracellular receptor α-DG is dispensable. They also demonstrated the anti-LASV effect of interferon-α and Ribavirin, and revealed the antiviral mechanism of Ribavirin.  

This study provides a new tool to study the LASV complete life cycle and to conduct antiviral screening and development in a BSL-2 laboratory.