Pathogenesis of the Old World Arenaviruses in Humans

Arenaviruses represent a fast-growing group of rodent-borne viruses (see Notes in the Proofs) which are an example of how environmental changes disrupt the natural animal virus–host balance and result in unexpected diseases. In the wild, arenaviruses exist as chronic infections in specific rodent hosts. This provides ideal conditions for competition within viral quasispecies for improved adaptation to the host. Analysis of arenavirus phylogeny and rodent cytochrome-b sequences provides examples of coevolution of arenaviruses with their rodent hosts. Based on their antigenic properties and geographic distribution approximately two dozen arenaviruses discovered so far are placed into two groups: the Old World (OW) or Lassa–LCMV complex and the New World (NW) or Tacaribe complex (Salvato et al., 2012). In general, the OW viruses are hosted by rodents of the family Muridae, subfamily Murinae. The NW arenaviruses are associated with rodents of the subfamily Sigmodontinae which are divided into the North and South American lineages. Phylogenetically the NW arenaviruses are further divided into clades A, B, C, and a recombinant A/B clade. Lymphocytic choriomeningitis virus (LCMV), the prototypic arenavirus that belongs to the OW group, is hosted by the house mouse (Mus musculus). The virus is distributed worldwide and can cause aseptic meningitis or meningoencephalitis in immunocompetent children and adults. Recent studies indicate that LCMV is also an under-recognized cause of congenital infection and neurological disease in the fetus and newborns (Bonthius, 2012; Laposova et al., 2013). In addition, LCMV and/or LCMVlike viruses have been also associated with clusters of fatal illness among tissue transplant recipients (Waggoner et al., 2013). All other human pathogens from the Arenaviridae cause viral hemorrhagic fevers (VHFs). The VHFs encompass a diverse group of viral infectious diseases of animals and humans caused by distinct RNA viruses from four major families. In humans these viruses can induce severe life-threatening diseases, with fever, malaise, hemorrhage, and hypovolemic shock resembling bacterial LPS (lipopolysaccharide)-induced sepsis-like shock at terminal stage of the diseases. The VHFs may occur as isolated case(s), such as imported case(s) from endemic areas, or may cause devastating lethal outbreaks (Goeijenbier et al., 2013; Ippolito et al., 2012; Moraz and Kunz, 2011; Vela, 2010). The Arenaviridae family contains the largest number of virus species causing VHFs. Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae responsible for several hundred thousand infections and death of thousands of patients with Lassa fever (LF) annually in West Africa (FichetCalvet and Rogers, 2009; Richmond and Baglole, 2003). Recently isolated in South Africa, LuJo virus (LUJV) will be a novel OW species (Briese et al., 2009). All pathogenic NW arenaviruses causing South American VHFs belong to clade B and include Junin virus (JUNV), Machupo virus (MACV), Guanarito virus (GTOV), Sabia virus (SABV), and the recently discovered Chapare virus (CHAPV) (Salvato et al., 2012). In addition to arenaviruses, causative agents of VHFs were found among Bunyaviridae (e.g., Crimean