Several arenaviruses cause hemorrhagic
fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus
vaccines are available, and current anti-arenavirus
therapy is limited to the use of
ribavirin, which is only partially effective and is associated with
anemia and other side effects. Therefore, it is important to develop effective
vaccines and better
antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced
arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and
trans-acting factors that control each of the steps of the arenavirus life cycle, including
RNA synthesis, packaging and budding. Knowledge derived from these studies is uncovering potential novel targets for therapeutic intervention, as well as facilitating the establishment of assays to identify and characterize candidate
antiviral drugs capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome and analyze their phenotypic expression would significantly contribute to the elucidation of arenavirus-host interactions, including the basis of their ability to cause severe HF. This, in turn, could lead to the development of novel, potent and safe arenavirus
vaccines.