Xapuri Virus, a Novel Mammarenavirus: Natural Reassortment and Increased Diversity Between New World Viruses
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Fernandes et al. Emerging Microbes & Infections (2018) 7:120 Emerging Microbes & Infections DOI 10.1038/s41426-018-0119-9 www.nature.com/emi ARTICLE Open Access Xapuri virus, a novel mammarenavirus: natural reassortment and increased diversity between New World viruses Jorlan Fernandes 1, Alexandro Guterres1, Renata Carvalho de Oliveira1, John Chamberlain2, Kuiama Lewandowski2, Bernardo Rodrigues Teixeira3,ThayssaAlvesCoelho1, Charle Ferreira Crisóstomo3,4,5, Cibele Rodrigues Bonvicino3,6, PauloSérgioD’Andrea3,5, Roger Hewson2 and Elba Regina Sampaio de Lemos1 Abstract Mammarenavirus RNA was detected in Musser’s bristly mouse (Neacomys musseri) from the Amazon region, and this detection indicated that rodents were infected with a novel mammarenavirus, with the proposed name Xapuri virus (XAPV), which is phylogenetically related to New World Clade B and Clade C viruses. XAPV may represent the first natural reassortment of the Arenaviridae family and a new unrecognized clade within the Tacaribe serocomplex group. Introduction choriomeningitis virus (LCMV) serocomplex, including Arenaviruses are bi-segmented ambisense RNA viruses viruses from Africa and, recently, Asia; and the New – hosted by rodents, bats, snakes, shrews, and ticks1 3. The World Tacaribe serocomplex, formed by viruses indi- 1,5–7 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Arenaviridae family currently comprises 41 viral species, genous to the Americas . classified into three genera, Mammarenavirus (35 spe- Despite the increased number of Old World viruses cies), Reptarenavirus (five species), and Hartmanivirus characterized in recent years3, New World mammar- (one specie)4. Each of the two arenavirus RNA segments enaviruses remain the most genetically diverse viral group encodes genes for two non-overlapping reading frames in within the family, composed of 18 species divided into ambisense polarity: the large (L) genomic segment for the four lineages: Clade A, Clade A-recombinant (Clade D), viral RNA-dependent RNA polymerase (RdRp or L pro- Clade B, and Clade C, according to their phylogenetic tein) and a zinc-binding matrix protein (Z protein), relationships1,5,7. Clades A and B include five (Allpahuayo, whereas the small (S) genomic segment encodes for the Flexal, Paraná, Pichindé, and Pirital) and seven (Amaparí, nucleocapsid protein (NP) and glycoprotein precursor Cupixi, Guanarito, Junín, Machupo, Tacaribe, and Sabiá) (GPC), which are post-translationally processed into the South American arenaviruses, respectively, regardless of envelope proteins G1 and G2 and the stable signal peptide the gene used for phylogenetic analysis7,8. Only Oliveros (SSP)1,5. and Latino viruses were identified in Clade C, regardless Mammarenaviruses were also classified into two of the gene sequence used for analysis5. Discrepancies groups according to their genomic features and antigenic were observed for mammarenaviruses indigenous to properties: the Old World Lassa-Lymphocytic North America (Tamiami, Whitewater Arroyo, and Bear Canyon viruses) and for a proposed new species from French Guiana. An analysis based on complete sequences Correspondence: Jorlan Fernandes (jorlan@ioc.fiocruz.br) or Elba Lemos (elba.lemos@ioc.fiocruz.br) confirms that the S RNA genome of these arenaviruses 1Laboratory of Hantaviruses and Rickettsiosis, Oswaldo Cruz Foundation, has a chimeric origin, likely a recombination event that – Oswaldo Cruz Institute, Rio de Janeiro RJ 21040-360, Brazil occurred in an ancestral virus9,10. These viruses form a 2National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK separate lineage known as Clade A/Rec and are proposed Full list of author information is available at the end of the article. © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Fernandes et al. Emerging Microbes & Infections (2018) 7:120 Page 2 of 10 to be named Clade D according to the latest updates in Table 1 Rodents captured in three localities from Acre arenaviruses taxonomy1. state, Brazil, 2015–2016, by species and locality The Amazon River Basin Region is a vast territory, Species Number of captured rodents encompassing nine South American countries: Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Porto Acre Rio Branco Xapuri Total Suriname, and Venezuela. This region contains the world’s largest tropical rainforest, with a climate char- Euryoryzomys macconelli ——11 acterized by high temperatures and humidity and copious Hylaeamys perenensis ——22 rainfall, and the most varied ecosystem in the world. — Favorable conditions exist for the transmission of Hylaeamys yunganus 1 12 numerous infectious agents, particularly from increasing Mesomys hispidus 1 — 12 contact of the human population to wild interface areas Neacomys musseri ——44 and because of accelerating population growth, environ- Neacomys spinosus 83617 mental, and climate changes11. In fact, the Amazon Basin — is often regarded as a hot spot for viruses and other Oecomys bicolor 72 9 pathogens that find optimal conditions to emerge or Oecomys sp. ——11 12 reinforce their pathogenic potential . Oligoryzomys microtis 13— 4 To date, three mammarenavirus were detected in the Proechimys brevicauda 2 ——2 Brazilian Amazon during surveys conducted in the 1960s: — Amaparí virus (Neacomys guianae), Cupixi virus (Oryz- Proechimys gardneri 11 2 omys megacephalus), and Flexal virus from an uni- Proechimys simonsi — 2 — 2 5,7,13,14 dentified oryzomyini rodent . Here, we report the Rhipidomys leucodactylus 1 ——1 identification of a novel mammarenavirus in Neacomys 22 11 16 49 musseri (Rodentia: Sigmodontinae) from the Amazon Basin Region; we propose that this mammarenavirus be designated as Xapuri virus (XAPV) after the locality where musseri virus and all other known mammarenavirus this new virus was detected. species, whereas a 38.5% aa sequence divergence was found for the entire NP (Table 2). Pairwise sequence Results comparison (PASC) was performed on both segments, A total of 49 rodents were analyzed: 22 from Porto Acre, and our sample was found to be most closely related to 16 from Xapuri, and 11 from Rio Branco localities; Latino (GenBank AF485259) and Oliveros (GenBank Neacomys spinosus (17) and Oecomys bicolor (9) were the NC_010248) viruses demonstrating 62.84–61.32% identity most abundant (Table 1). Amplification of the partial for the S segment, whereas the L segment showed GPC gene was observed for one Neacomys musseri (1/ 57.35–55.71% identity with Amaparí (GenBank 49–2.0%) male collected in 2015, in the Seringal AY924389) and Guanarito viruses (GenBank NC005082). Cachoeira locality, Xapuri municipality (Fig. 1). In the maximum likelihood (ML) and Bayesian phylo- Complete genome sequencing of Neacomys musseri genetic analyses for the S and L segments, the Amazonian mammarenavirus included two segments: the L segment virus described in this study formed an independent clade (GenBank MG976577) of 7049 nucleotides (nt) and the S closely related to Clades C and B New World mammar- segment (GenBank MG976578) of 3405 nt. Each segment enaviruses, respectively (Figs. 3 and 4). Sequences from encoded two open reading frames (ORFs) in an ambisense NP, Z, and L proteins displayed the same topology as the organization with an intergenic region of 72 and 88 nt in L segment, taking a stem lineage position for New World length containing a predicted hairpin between the ORFs Clade B viruses (Fig. 5). GPC was the most divergent for the S and L segment, respectively. NP, GPC, Z, and L protein, forming a sister stem lineage clade with New protein lengths were 557 amino acids (aa), 512, 96, and World Clade C viruses (Fig. 5). Bootscan and RDP4 2199 aa, respectively (Fig. 2). Additional features com- recombination analysis of S and L segment sequences by monly observed in mammarenavirus genomes include the Simplot revealed no recombination peaks. Reconstructed conservation of the 3′−5′ termini and the presence of an phylogenetic trees, including the complete nt GPC gene L-domain motif within the Z protein. show no alternate clustering of the N. musseri virus and Deduced aa and nt sequences from the four proteins Clade C viruses. and complete S and L segments were compared to those of other representative mammarenaviruses. Nucleotide Discussion sequence divergences of >34.8 and >41.2% for the S and L The genus Neacomys Thomas, 1900 (Cricetidae, Sig- segments, respectively, were found between the Neacomys modontinae, Oryzomyini) comprises eight valid species Fernandes et al. Emerging Microbes & Infections (2018) 7:120 Page 3 of 10 Fig. 1 Municipalities of Acre state, Brazil, in which rodents were captured of spiny rats, distributed from Central and South Viruses (ICTV)1 also includes