Reverse genetics approaches for the development of mammarenavirus live-attenuated vaccines

Several mammarenaviruses can cause severe hemorrhagic fever disease with a very high case fatality rate, representing important threats to human health within the viruses' endemic regions. To date, there are no United States (US) Food and Drug Administration (FDA)-licensed vaccines available to combat mammarenavirus infections in humans, and current anti-mammarenavirus therapy is limited to off-label use of the guanosine analog ribavirin, which has limited efficacy and has been associated with significant side effects. Vaccination is one of the most effective ways to prevent viral diseases, and live-attenuated vaccines (LAVs) have been shown to often provide long-term protection against a subsequent natural infection by the corresponding virulent form of the virus. The development of mammarenavirus reverse genetics systems has provided investigators with a powerful approach for the investigation of the molecular and cell biology of mammarenaviruses and also for the generation of recombinant viruses containing predetermined mutations in their genome for their implementation as LAVs for the treatment of mammarenavirus infections. In this review, we summarize the current knowledge on the mammarenavirus molecular and cell biology, and the use of reverse genetic approaches for the generation of recombinant mammarenaviruses. Moreover, we briefly discus some novel LAV approaches for the treatment of mammarenavirus infections based on the use of reverse genetics approaches.