Abstract
Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions. To date, no Food and Drug Administration (FDA)-licensed vaccines are available to combat human arenavirus infections, and current anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetic approaches has provided investigators with a novel and powerful approach for the study of arenavirus biology including virus–host interactions underlying arenavirus induced disease. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription, as well as particle assembly and budding. Likewise, it is now feasible to rescue infectious arenaviruses containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis. The use of reverse genetics approaches has also allowed the generation of recombinant arenaviruses expressing additional genes of interest. These advances in arenavirus molecular genetics have also facilitated the implementation of novel screens to identify anti-arenaviral drugs, and the development of novel strategies for the generation of arenavirus live-attenuated vaccines. In this review, we will summarize the current knowledge on reporter-expressing, replicating-competent arenaviruses harboring reporter genes in different locations of the viral genome and their use for studying and understanding arenavirus biology and the identification of anti-arenaviral drugs to combat these important human pathogens.
Highlights
Several arenaviruses cause hemorrhagic fever (HF) disease in humans and pose an important public health problem in their endemic regions
Arenavirus gene transcription is mediated by the viral genome and antigenome promoters located within the untranslated regions (UTRs) at the 31 termini of viral RNA and complementary
The development of reverse genetics systems to generate infectious recombinant arenaviruses from plasmid DNA has significantly advanced the investigation of arenavirus biology [1,42], including the characterization of cis-acting and the trans-acting factors that control each of the different steps of the arenavirus infectious life cycle [92,93,94,95]
Summary
Arenaviruses are bi-segmented negative-sense, single-stranded, RNA viruses that belong to the Arenaviridae family (Figure 1) [1]. Protease (S1P) to yield the two mature virion glycoproteins (GP1 and GP2) that form the spikes that encodes the viral nucleoprotein (NP) (Figure 1A, green) that encapsidates the viral RNA, and together decorate the virus surface and mediate receptor recognition and cell entry [1,46,47,48]. L viral and nucleoprotein the viral RNA, viral ribonucleoproteins encodes the (NP)constitute (Figure 1A,the green) that encapsidates the viral(vRNPs), RNA, and which are the minimal factors involved in arenavirus genome replication gene transcription [1,49,50]. The Small (S) RNA segment (3.5 kb, top) encodes the viral glycoprotein precursor (GPC, purple) and nucleoprotein (NP, green). Associated with the vRNPs is the L polymerase protein that, together with NP, are the minimal components for viral genome replication and gene transcription
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