Mammarenavirus Genetic Diversity and Its Biological Implications

Members of the family Arenaviridae are classified into four genera: Antennavirus, Hartmanivirus, Mammarenavirus, and Reptarenavirus. Reptarenaviruses and hartmaniviruses infect (captive) snakes and have been shown to cause boid inclusion body disease (BIBD). Antennaviruses have genomes consisting of 3, rather than 2, segments, and were discovered in actinopterygian fish by next-generation sequencing but no biological isolate has been reported yet. The hosts of mammarenaviruses are mainly rodents and infections are generally asymptomatic. Current knowledge about the biology of reptarenaviruses, hartmaniviruses, and antennaviruses is very limited and their zoonotic potential is unknown. In contrast, some mammarenaviruses are associated with zoonotic events that pose a threat to human health. This review will focus on mammarenavirus genetic diversity and its biological implications. Some mammarenaviruses including lymphocytic choriomeningitis virus (LCMV) are excellent experimental model systems for the investigation of acute and persistent viral infections, whereas others including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa fever (LF) and Argentine hemorrhagic fever (AHF), respectively, are important human pathogens. Mammarenaviruses were thought to have high degree of intra-and inter-species amino acid sequence identities, but recent evidence has revealed a high degree of mammarenavirus genetic diversity in the field. Moreover, closely related mammarenavirus can display dramatic phenotypic differences in vivo. These findings support a role of genetic variability in mammarenavirus adaptability and pathogenesis. Here, we will review the molecular biology of mammarenaviruses, phylogeny, and evolution, as well as the quasispecies dynamics of mammarenavirus populations and their biological implications.