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Arenavirus Genomics: Novel Insights Into Viral Diversity, Origin, and Evolution

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Arenavirus Genomics: Novel Insights Into Viral Diversity, Origin, and Evolution Available online at www.sciencedirect.com ScienceDirect Arenavirus genomics: novel insights into viral diversity, origin, and evolution 1 1 Chiara Pontremoli , Diego Forni and Manuela Sironi Next-generation sequencing technologies have revolutionized about arenavirus diversity, evolution, origin, and host our knowledge of virus diversity and evolution. In the case of association. arenaviruses, which are the focus of this review, metagenomic/ metatranscriptomic approaches identified reptile-infecting and An expanding family with remarkable genome fish-infecting viruses, also showing that bi-segmented plasticity genomes are not a universal feature of the Arenaviridae family. Since 1976 and until 2012 the Arenaviridae family com- Novel mammarenaviruses were described, allowing inference prised a single genus of mammal-infecting viruses now of their geographic origin and evolutionary dynamics. Extensive known as Mammarenavirus. Most mammarenaviruses sequencing of Lassa virus (LASV) genomes revealed the have natural reservoirs in rodents and were historically zoonotic nature of most human infections and a Nigerian origin divided into two monophyletic groups: the Old World of LASV, which subsequently spread westward. Future efforts (OW) and the New World (NW) complexes (Figure 1). will likely identify many more arenaviruses and hopefully provide insight into the ultimate origin of the family, the In 2009, several snakes hosted in an aquarium in San pathogenic potential of its members, as well as the Francisco were diagnosed with a fatal condition known as determinants of their geographic distribution. inclusion body disease (IBD). The availability of unbi- ased methods for pathogen identification, the first repre- sentative of which was the Virochip DNA microarray Address technology [5], spurred the search for the infectious agent Scientific Institute, IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio (see https://www.ucsf.edu/news/2012/08/12545/ Parini, Lecco, Italy mysterious-snake-disease-decoded for a narration of the events). Eventually, in 2012–2013, metagenomic analyses Corresponding author: Sironi, Manuela ([email protected]) 1 These authors contributed equally to this work. led to the sequencing and subsequent isolation of novel arenaviruses from captive alethinophidian snakes suffer- Current Opinion in Virology 2019, 34:18–28 ing from IBD [6–8]. These works resulted in the estab- Reptarenavirus Hart- This review comes from a themed issue on Viral immunology lishment of two novel genera ( and manivirus) in the Arenaviridae family [9 ] (Figure 1). Edited by Juan C de la Torre and John Teijaro For a complete overview see the Issue and the Editorial Mammarenaviruses, reptarenaviruses, and hartmani- Available online 27th November 2018 viruses have characteristic bi-segmented genomes with https://doi.org/10.1016/j.coviro.2018.11.001 ambisense organization. The small segment (S) encodes 1879-6257/ã 2018 Elsevier B.V. All rights reserved. the glycoprotein precursor (GPC) and the nucleocapsid protein (NP); the large segment (L) codes for the RNA- dependent RNA polymerase (L) and, in the case of mammarenaviruses and reptarenaviruses, for a zinc-bind- ing protein (Z) (Figure 2a). During the life cycle of mammarenaviruses, the matrix Z-protein participates to Introduction different processes, including the formation of infectious In recent years, the advent of metagenomic and meta- viral particles and viral budding [10–15]. Current evi- transcriptomic approaches resulted in the identification of dence however suggests that hartmaniviruses lack a Z an outstanding number of novel viruses (e.g., [1 ,2 ]). protein [16 ], indicating that arenaviruses may have Also, next-generation technologies have allowed the rapid evolved diverse mechanisms of virion assembly and cell sequencing of multiple genomes of known viruses. For egress. instance, the sequencing of Ebola virus (EBOV) and Lassa virus (LASV) from infected patients/animals has Also, very recent work showed that a bi-segmented provided invaluable information about the genetic diver- genome is not a universal feature of arenaviruses. A sity and evolutionary dynamics of these human pathogens large-scale metatranscriptomic study of RNA viruses in [3 ,4]. In this review, we focus on Arenaviridae, a family cold-blooded vertebrates identified a plethora of novel of negative-sense RNA viruses which includes LASV. We viruses, including two frogfish (Antennarius striatus) are- discuss how next-generation approaches and genome naviruses with tri-segmented genomes (Figures 1 and 2a) sequencing in general have expanded our knowledge [2 ]. Based on sequence similarity and phylogenetic Current Opinion in Virology 2019, 34:18–28 www.sciencedirect.com Arenavirus diversity, origin, and evolution Pontremoli, Forni and Sironi 19 Figure 1 (a) 0.99 AMAV 1 GTOV CUPXV 1 CHAPV 1 SBAV 1 JUNV 1 1 1 MACV TCRV 1 LATV OLVV 1 0.80 ALLV 1 PICHV 1 PIRV 0.80 FLEV 1 PRAV BCNV 1 0.95 TMMV WWAV Mammarenavirus 1 GAIV 0.84 MOBV 1 LUAV 1 MORV 1 0.99 IPPYV 1 SOLV 1 1 LASV MRLV 0.93 1 LORV WENV 1 1 MRWV 1 OKAV 0.99 LCMV 1 1 RYKV 0.99 LNKV SOUV 0.48 LUJV CASV 1 1 GOGV 1 ROUTV Reptarenavirus 1 TSMV-2 1 UGV-1 0.90 HISV Hartmanivirus 1 WLFV-1 WLFV-2 Antennavirus Hubei myriapoda virus 5 0.2 subs/site (b) 1 ALLV 1 PICHV 1 PIRV 1 FLEV 1 PRAV BCNV 1 0.99 TMMV WWAV 1 AMAV 1 1 GTOV CUPXV 0.99 1 JUNV 1 MACV 1 TCRV 1 CHAPV 1 SBAV LATV 1 OLVV Mammarenavirus 1 GAIV 1 1 MOBV 0.99 LUAV 1 MORV 1 LASV 1 LORV 1 WENV 0.99 IPPYV 0.99 1 SOLV MRLV 1 1 MRWV OKAV 1 1 LCMV 1 RYKV 0.99 LNKV 0.97 SOUV 1 LUJV CASV 1 1 GOGV 1 UGV-1 Reptarenavirus 1 TSMV-2 ROUTV HISV Hartmanivirus 0.99 1 WLFV-1 WLFV-2 Antennavirus 0.2 subs/site Current Opinion in Virology Phylogenetic relationships for the Arenaviridae family. Maximum clade credibility tree of (a) the RdRp domain and (b) the NP protein. Only ICTV (International Committee on Taxonomy of Viruses)- approved viral species are included, plus the Hubei myriapoda virus 5 for the RdRp tree. Trees were obtained with BEAST (version 2.4.4) [64] and numbers indicate the node posterior probability. A list of species and virus abbreviations is reported in Supplementary Table 1. www.sciencedirect.com Current Opinion in Virology 2019, 34:18–28 20 Viral immunology Figure 2 (a) L segment S segment Mammarenavirus Z L RdRp GPC NP L segment S segment Reptarenavirus Z L RdRp NP GP Filovirus-like L segment S segment Hartmanivirus L (partial) RdRp GPC NP Z? L segment M segment S segment Antennavirus L RdRp GPC NP hypothetical protein segment 1 segment 2 segment 3 putative putative RdRp Hubei myriapoda virus 5 L GPC NP (b) Structural prediction HISV GPC 277 304 JUNV GPC 446 471 Known structure Current Opinion in Virology Arenavirus genome organization and sequence similarity. (a) Arenavirus genome organization is schematically shown together with information on sequence homology. Homologous regions are indicated in the same color; however, color codes and color intensity are arbitrary and not indicative of the level of sequence similarity. Gray indicates regions 2 that display no homology to known proteins outside the genus (as assessed by BLASTp, HHpred and Phyre ) [65–67]. (b) Sequence/structural 2 2 homology between HISV and Junı`n virus glycoproteins as detected by Phyre (very similar results were obtained with HHpred, not shown). Phyre predicted JUNV GPC (PDB ID: 2L0Z) as the best match with a confidence of 93.3%. The amino acid alignment is shown with residues colored on the basis of physico-chemical properties. Known and predicted secondary structures are also indicated (H: helix, E: extended strand in b-sheet conformation, C: coil, T: hydrogen bonded turn, B: residue in isolated b-bridge, S: bend). Current Opinion in Virology 2019, 34:18–28 www.sciencedirect.com Arenavirus diversity, origin, and evolution Pontremoli, Forni and Sironi 21 relationships, the frogfish viruses were proposed to form a short protein region, was with Junı`n virus (JUNV, a new genus (Antennavirus) in the Arenaviridae family mammarenavirus) glycoprotein (Figure 2b), whereas no (https://talk.ictvonline.org/files/proposals/ detectable homology was found with filovirus sequences. animal_dsrna_and_ssrna-_viruses/m/ This suggests that an ancient recombination event with a animal_rna_minus_ec_approved). Interestingly, large filovirus-like ancestor occurred on the lineage leading to scale analyses in invertebrates also identified arenavi- reptarenaviruses. However, the evolutionary origin of rus-like sequences: the so called Hubei myriapoda virus arenavirus glycoproteins awaits clarification, as no signifi- 5 [1 ] shows sequence similarity to arenavirus L proteins cant homology with known proteins could be detected for and has a tri-segmented genome (Figures 1a and 2 a). the putative GPC sequence of fish arenaviruses, which Whereas it is presently impossible to determine whether show homologous regions with other arenaviruses for the the arenavirus ancestor had a tri-segmented or bi-seg- L and NP proteins [2 ] (Figure 2a). mented genome, differences in genome organization indicate plasticity in terms of segment number and, to Host associations a lesser extent, gene content (Figure 2a). Metagenomic A general concept that emerged from large-scale meta- analyses of reptarenavirus-infected snakes also uncovered transcriptomic analyses is that, over long time frames, the an unexpected aspect of arenavirus genomic diversity: the associations between RNA viruses and their vertebrate very frequent occurrence of mixed infections and the hosts tend to be stable, despite frequent host-shifts [2 ]. different representation of S and L segment genotypes In the case of arenaviruses, though, long-term associations [16 ,17,18 ]. Typically, infected reptiles harbor multiple are difficult to establish, as the hartmanivirus NP and L S and/or L segment genotypes and, in individual snakes, genes seem to be more closely related to those of fish L segment genotypes tend to outnumber S segment arenaviruses than to reptarenaviruses (Figure 1).
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