Pathogenic arenaviruses: Lujo and Guanarito viruses

The arenaviruses are a large and diverse group of viruses that share a common genetic structure, with all possessing a genome that comprises two separate RNA molecules of negative sense. Arenaviruses are zoonotic viruses, and each has evolved to occupy a specific rodent host. Humans become infected when they come into close contact with these infected rodents, through the inhalation of rodent excreta. Interestingly, recent evidence shows that arenaviruses have also established reservoirs in a variety of reptiles, a finding that poses interesting evolutionary questions. Lassa virus (LASV) is perhaps the most notorious arenavirus, and is responsible for continued outbreaks in central Africa, and causes several thousand human fatalities per year due to a devastating hemorrhagic fever. The highly lethal Lujo virus (LUJV) has recently been identified in South Africa, and like LASV, it is associated with several cases of hemorrhagic fever, with an exceptionally high case/fatality rate. We are interested in understanding the structure-function relationship of proteins of arenaviruses, as well as understanding how these components affect host cell processes. This work involves a broad range of techniques, including mammalian cell culture, recombinant protein expression and the structural biology techniques of electron microscopy and crystallography. To facilitate this work, we also work with so-called ‘model’ arenaviruses that are relatively safe to work with under more conventional containment conditions, and these include lymphocytic choriomeningitis virus (LCMV) and Pichinde virus. Work on arenaviruses is funded by The MRC, as well as continued support from Public Health England (formerly Health Protection Agency - HPA) in collaboration with Dr Roger Hewson, the Scientific Programme Leader for Viral Hemorrhagic fever Viruses, at the PHE site at Porton Down.