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In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Mammarenaviruses (genus Mammarenavirus , family Arenaviridae ) are rodent-borne zoonotic viruses consisting of 52 viral species, including ten that are pathogenic to humans. Currently, only two endemic mammarenavirus species are known in Europe: the human pathogenic Mammarenavirus choriomeningitidis (LCMV) and the recently discovered hedgehog-origin Mammarenavirus mecsekense (MEMV). In this study, 59 faecal specimens from Northern white-breasted hedgehogs ( Erinaceus roumanicus ) from different geographic regions in Hungary were investigated for mammarenavirus presence and complete genome characterization using newly designed screening primers by RT-semi-nested PCR and sequencing methods. Five (8.5%) of the 59 samples tested positive for mammarenavirus RNA (ER8, ER15, ER27, ER33, and ER39, GenBank accession numbers PQ441959-PQ441968). The L- and S-segments of these strains showed 66–93% and 73–92% nt identity to the closest known mammarenavirus, MEMV, respectively. The NP protein exhibited 86–97% aa sequence identity compared to the corresponding protein of MEMV. Notably, the S-segment intergenic region (S-IGR) of strains ER8, ER15, ER27 and ER33 exceeded the average nt length among known mammarenaviruses and contained two, highly similar stem-loop structures with conserved self-complementary nucleotide motifs. Based on the sequence- and phylogenetic analysis these strains (ER8, ER15, ER27 and ER33) potentially represent a novel mammarenavirus species, tentatively named Pannonia mammarenavirus (PANV).

Mammarenaviruses are noteworthy zoonotic pathogens, and the main reservoirs are rodent species. We report the detection of a novel mammarenavirus in 6/183 (3.3%) in necropsied European hedgehogs (Erinaceus europaeus) collected in Italy. The whole-genome sequence obtained for 4 strains revealed a marked genetic diversity but a monophyletic origin.

Southeastern Asia is a recognised hotspot for emerging infectious diseases, many of which have an animal origin. Mammarenavirus infections contribute significantly to the human disease burden in both Africa and the Americas, but little data exists for Asia. To date only two mammarenaviruses, the widely spread lymphocytic choriomeningitis virus and the recently described Wēnzhōu virus have been identified in this region, but the zoonotic impact in Asia remains unknown. Here we report the presence of a novel mammarenavirus and of a genetic variant of the Wēnzhōu virus and provide evidence of mammarenavirus-associated human infection in Asia. The association of these viruses with widely distributed mammals of diverse species, commonly found in human dwellings and in peridomestic habitats, illustrates the potential for widespread zoonotic transmission and adds to the known aetiologies of infectious diseases for this region. Rodents have long been notorious for spreading disease among humans. Often the animals can carry viruses and transmit them to humans without becoming ill. Certain species thrive in cities and agricultural areas where they come in close contact with humans; this creates many opportunities to spread infection. As humans urbanize and farm larger swaths of previously wild lands, the risk of rodent-transmitted infections increases. As a result, some scientists are working to identify viruses carried by rodents in human settlements and hopefully prevent them from spreading to humans. The mammarenavirsuses are a group of rodent-transmitted viruses that commonly cause illness in people in Africa and Latin America. Each year, one such virus – the Lassa virus –sickens as many as 300,000 people in Africa and kills 5,000. So far, only two mammarenaviruses have been found in Asia: one called the Wēnzhōu virus and another called LCMV. However only LCMV is known to cause human illness and many cases of illness caused by mammarenaviruses in Asia may go undetected because they often cause mild symptoms similar to the common cold. Blasdell et al. have now tested lung samples from 20 species of rodents collected at 7 sites in Cambodia, Thailand, and Laos to look for molecules produced by mammarenaviruses. The tests revealed a strain of Wēnzhōu virus circulating in Cambodian rats that often live in urban areas. A new mammarenavirus was also detected in rodents that live in Thai rice fields. However, infecting wild and domestic rodents with the viruses in the laboratory did not cause many noticeable signs of illness. Blasdell et al. then tested samples from Cambodian patients who either had influenza-like symptoms or more serious symptoms that are associated with a condition called Dengue fever (which is common in the area). Some patients with respiratory symptoms tested positive for the Wēnzhōu virus. Because the symptoms are mild and similar to those of other common diseases it is likely that the Wēnzhōu virus may be spreading more widely among humans in Asia. The next challenges are to provide a better estimate of the frequency of this disease in the human population in Asia and to describe the full spectrum of disease that might be associated with this newly discovered infectious disease.

Viruses need cells for their replication and, therefore, ways to hijack cellular functions. Mitochondria play fundamental roles within the cell in metabolism, immunity and regulation of homeostasis due to which some viruses aim to alter mitochondrial functions. Herein we show that the nucleoprotein (NP) of arenaviruses enters the mitochondria of infected cells, affecting the mitochondrial morphology. Reptarenaviruses cause boid inclusion body disease (BIBD) that is characterized, especially in boas, by the formation of cytoplasmic inclusion bodies (IBs) comprising reptarenavirus NP within the infected cells. We initiated this study after observing electron-dense material reminiscent of IBs within the mitochondria of reptarenavirus infected boid cell cultures in an ultrastructural study. We employed immuno-electron microscopy to confirm that the mitochondrial inclusions indeed contain reptarenavirus NP. Mutations to a putative N-terminal mitochondrial targeting signal (MTS), identified via software predictions in both mamm- and reptarenavirus NPs, did not affect the mitochondrial localization of NP, suggesting that it occurs independently of MTS. In support of MTS-independent translocation, we did not detect cleavage of the putative MTSs of arenavirus NPs in reptilian or mammalian cells. Furthermore, in vitro translated NPs could not enter isolated mitochondria, suggesting that the translocation requires cellular factors or conditions. Our findings suggest that MTS-independent mitochondrial translocation of NP is a shared feature among arenaviruses. We speculate that by targeting the mitochondria arenaviruses aim to alter mitochondrial metabolism and homeostasis or affect the cellular defense.

In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated with land use changes, which favor abundance of generalist rodent species. In the Americas—where the rates of land use change are among the highest worldwide—at least 1326 of all 2277 known rodent species have been reported. We conducted a literature review of studies between 1960 and 2020, to establish the current and historical knowledge about genotypes of mammarenaviruses and their rodent reservoirs in the Americas. Our overall goal was to show the importance of focusing research efforts on the American continent, since the conditions exist for future viral hemorrhagic fever (VHF) outbreaks caused by rodent-borne viruses, in turn, carried by widely distributed rodents. We found 47 species identified down to the species level, and one species identified only down to the genus level (Oryzomys sp.), reported in the Americas as reservoirs of mammarenaviruses, most these are ecological generalists. These species associate with 29 genotypes of Mammarenavirus, seven of which have been linked to VHFs in humans. We also highlight the need to monitor these species, in order to prevent viral disease outbreaks in the region.

Rodents are a speciose group of mammals with strong zoonotic potential. Some parts of Africa are still underexplored for the occurrence of rodent-borne pathogens, despite this high potential. Angola is at the convergence of three major biogeographical regions of sub-Saharan Africa, each harbouring a specific rodent community. This rodent-rich area is, therefore, strategic for studying the diversity and evolution of rodent-borne viruses. In this study we examined 290 small mammals, almost all rodents, for the presence of mammarenavirus and hantavirus RNA. While no hantavirus was detected, we found three rodent species positive for distinct mammarenaviruses with a particularly high prevalence in Namaqua rock rats (Micaelamys namaquensis). We characterised four complete virus genomes, which showed typical mammarenavirus organisation. Phylogenetic and genetic distance analyses revealed: (i) the presence of a significantly divergent strain of Luna virus in Angolan representatives of the ubiquitous Natal multimammate mouse (Mastomys natalensis), (ii) a novel Okahandja-related virus associated with the Angolan lineage of Micaelamys namaquensis for which we propose the name Bitu virus (BITV) and (iii) the occurrence of a novel Mobala-like mammarenavirus in the grey-bellied pygmy mouse (Mus triton) for which we propose the name Kwanza virus (KWAV). This high virus diversity in a limited host sample size and in a relatively small geographical area supports the idea that Angola is a hotspot for mammarenavirus diversity.

Mammarenaviruses cause chronic infections in rodents, which are their predominant natural hosts. Human infection with some of these viruses causes high-consequence disease, posing significant issues in public health. Currently, no FDA-licensed mammarenavirus vaccines are available, and anti-mammarenavirus drugs are limited to an off-label use of ribavirin, which is only partially efficacious and associated with severe side effects. Dihydroorotate dehydrogenase (DHODH) inhibitors, which block de novo pyrimidine biosynthesis, have antiviral activity against viruses from different families, including Arenaviridae, the taxonomic home of mammarenaviruses. Here, we evaluate five novel DHODH inhibitors for their antiviral activity against mammarenaviruses. All tested DHODH inhibitors were potently active against lymphocytic choriomeningitis virus (LCMV) (half-maximal effective concentrations [EC50] in the low nanomolar range, selectivity index [SI] > 1000). The tested DHODH inhibitors did not affect virion cell entry or budding, but rather interfered with viral RNA synthesis. This interference resulted in a potent interferon-independent inhibition of mammarenavirus multiplication in vitro, including the highly virulent Lassa and Junín viruses.

Arenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Junín and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC. The virion is endocytosed on binding to a cell-surface receptor, and membrane fusion is initiated in response to physiological acidification of the endosome. As with other class I virus fusion proteins, GPC-mediated membrane fusion is promoted through a regulated sequence of conformational changes leading to formation of the classical postfusion trimer-of-hairpins structure. GPC is, however, unique among the class I fusion proteins in that the mature complex retains a stable signal peptide (SSP) as a third subunit, in addition to the canonical receptor-binding and fusion proteins. We will review the curious properties of the tripartite GPC complex and describe evidence that SSP interacts with the fusion subunit to modulate pH-induced activation of membrane fusion. This unusual solution to maintaining the metastable prefusion state of GPC on the virion and activating the class I fusion cascade at acidic pH provides novel targets for antiviral intervention.