Multifunctional noncoding regions in the mammarenavirus genome

Mammarenaviruses often cause long-term asymptomatic chronic infections in their natural hosts, primarily rodents, and include several human pathogens responsible for diseases ranging from mild febrile illnesses to life-threatening hemorrhagic fever. Mammarenaviruses encode two genes in each segment of their bisegmented RNA genome, with ambisense polarity. The multifunctionality of each gene product supports the optimal propagation of the virus. Moreover, the noncoding regions of the mammarenaviral genome have been shown to have multiple functions, beyond the control of viral transcription and replication. For instance, the noncoding intergenic region (IGR) is integral to the posttranscriptional regulation of viral protein expression. This mechanism underlies the efficient multiplication of the virus, which utilizes an ambisense coding strategy. Further clarification of the multifunctionality of the noncoding regions of the mammarenaviral genome will extend our understanding of the complex biology of these simple viruses and provide the basis for the development of novel medical countermeasures.