Structural and functional studies of Lassa fever virus replication and transcription

Lassa fever virus infects more than 300,000 people and kills 5,000 people every year in South Africa. There is no vaccine and effective drug available, and the infection can spread from person to person, which is a great threat to human health. We have determined the first crystal structure of the nucleoprotein of Lassa fever virus, revealed that the nucleoprotein of Lassa fever virus not only involves in protection the viral genomic RNA, RNA replication and transcription, but also has functions in immune suppression (Nature). Although Lassa fever RNA-dependent polymerase (L protein) and nucleoprotein (NP) are reported to form replication machinery for RNA transcription and replication. However, Lassa fever virus RNA transcription and replication by which mechanisms are unclear. To understand the transcription and replication in molecular level, this exciting project is going to express and purify both L protein and NP protein, and reconstitute the replication machinery in vitro for activity assays, and determine the crystal structure of the replication complex.

Lassa fever virus belongs to Arenavirus family, which has more than 21 members. Among these members, at least six of them cause severe diseases with high mortality and morbidity, and new members emerge. The work will be very important for develop new vaccines and drugs.