Arenaviruses

Abstract The arenaviruses are a large and diverse group of enveloped ribonucleic acid (RNA) viruses that merit significant attention as powerful experimental models and important human pathogens. The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has been instrumental in many landmark studies on virus–host interaction and antiviral immunity. Several arenaviruses, including Lassa virus in Africa and the South American arenaviruses such as Junin virus , Guanarito virus , Machupo virus and Sabia virus cause severe viral haemorrhagic fevers in humans and represent serious public health problems. Arenavirus haemorrhagic fevers are among the most devastating emerging human diseases with high fatality rates in hospitalized patients and a limited therapeutic repertoire available. Moreover, compelling evidence indicates that the worldwide‐distributed LCMV is a neglected human pathogen of clinical significance, especially in cases of congenital infection and immunocompromised individuals, as tragically illustrated by recent fatal cases of transplant‐associated infections. Key concepts Arenaviruses are zoonotic pathogens that are carried in nature by persistent infection of rodent hosts. The interaction of prototypic arenavirus LCMV with its host species, the mouse, provided fundamental concepts in virology and immunology. The current diversity of arenaviruses is the result of a remarkable long‐term co‐evolution between the viruses and their rodent hosts. When infecting humans as accidental hosts, some arenaviruses cause severe haemorrhagic fevers with high mortality. Arenavirus haemorrhagic fevers belong to the worst human diseases and represent important public health problems in many regions of the developing world. The epidemiology, clinical disease, diagnostics and current treatment for these diseases will be discussed. During the past decade much has been learned about the molecular and cell biology of the arenavirus life cycle. Cellular receptors for all major human pathogenic arenaviruses have been identified and first light has been shed on their mechanisms of cell entry. The advent of a powerful reverse genetic system for arenaviruses has allowed to elucidate the mechanisms of arenavirus replication, gene expression and assembly and release of progeny virions from infected cells. The investigation of the fundamental virology of arenaviruses will likely provide novel avenues for the development of efficacious therapeutic strategies against these important human pathogens.