The board is set , the pieces are moving : Modulation of New World arenavirus entry by host proteins

摘要

Arenaviruses are enveloped viruses with 2 ambisense genomic RNA molecules, whose entry into cells is mediated by the viral glycoprotein (GP), generated by proteolytic processing of the precursor GPC into the subunits GP1 (the receptor-binding domain), GP2 (the transmembrane fusion protein), and the stable signal peptide [1]. The family Arenaviridae has been historically represented by a single genus, now named Mammarenavirus, members of which are carried by rodent species endemic to the geographic area in which the viruses are found. Recently, the number of genera in this family has expanded to include arenaviruses that infect snakes (Reptarenavirus and Hartmanivirus) and fish (Antennavirus) [2]. The Mammarenaviruses are classified into 2 groups: The Tacaribe (New World) serocomplex includes viruses endemic to the Americas, while the Lassa–lymphocytic choriomeningitis serocomplex (Old World) includes viruses indigenous to Africa and Asia, as well as lymphocytic choriomeningitis virus (LCMV), now found worldwide [3]. Members of both complexes are transmitted to humans through direct contact or by inhalation of aerosolized rodent excreta [4]. The New World arenaviruses (NWAs) Jun?′n (JUNV), Machupo (MACV), Sabia′, Chapare, and Guanarito cause hemorrhagic fevers in humans, with about 30% case fatality rate in untreated individuals. A highly effective live-attenuated vaccine for JUNV, the causal agent of Argentinean Hemorrhagic Fever (AHF), has greatly decreased disease incidence in Argentina, although there have been recent discussions about decreasing vaccine production because of low infection rates [5]. Plasma therapy reduces JUNV fatality rates to 1%, but due to the effective vaccination effort, there are now declining numbers of convalescent plasma donors [6]. While only a handful of NWAs are associated with human disease, there are 40 species of rodents harboring 25 NWAs throughout North and South America, and there is a possibility for the emergence of other NWA as zoonoses into humans [3]. Thus, there is still a need for a better understanding of NWA infection and the development of anti-arenavirus therapeutics.