S RNA Intergenic Deletions Drive Viral Interference during Arenavirus Infections.

Arenaviruses are hemorrhagic fever-causing pathogens that infect millions of people a year. There are currently no approved antivirals that target arenaviruses and understanding natural mechanisms that inhibit arenavirus replication is crucial for the development of effective therapeutics. Here, we identify multiple deletions within arenavirus genomes that are associated with the inhibition of viral replication. We show that these deletions prevent viral protein production through the removal of the intergenic region of the viral genome. These deletions were found in all arenaviruses tested in this study representing a novel mechanism for development of new antivirals and vaccines that broadly target the arenavirus family.