Hantaviruses: rediscovery and new beginnings

Abstract

Virus and host gene phylogenies, indicating that antigenically distinct hantaviruses (family Bunyaviridae, genus Hantavirus) segregate into clades, which parallel the molecular evolution of rodents belonging to the Murinae, Arvicolinae, Neotominae and Sigmodontinae subfamilies, suggested co-divergence of hantaviruses and their rodent reservoirs. Lately, this concept has been vigorously contested in favor of preferential host switching and local host-specific adaptation. To gain insights into the host range, spatial and temporal distribution, genetic diversity and evolutionary origins of hantaviruses, we employed reverse transcription-polymerase chain reaction to analyze frozen, RNAlater(®)-preserved and ethanol-fixed tissues from 1546 shrews (9 genera and 47 species), 281 moles (8 genera and 10 species) and 520 bats (26 genera and 53 species), collected in Europe, Asia, Africa and North America during 1980-2012. Thus far, we have identified 24 novel hantaviruses in shrews, moles and bats. That these newfound hantaviruses are geographically widespread and genetically more diverse than those harbored by rodents suggests that the evolutionary history of hantaviruses is far more complex than previously conjectured. Phylogenetic analyses indicate four distinct clades, with the most divergent comprising hantaviruses harbored by the European mole and insectivorous bats, with evidence for both co-divergence and host switching. Future studies will provide new knowledge about the transmission dynamics and pathogenic potential of these newly discovered, still-orphan, non-rodent-borne hantaviruses.

Keywords: Chiroptera; Evolution; Hantavirus; Soricomorpha.

Figure 1

Global landscape of representative rodent-borne hantaviruses and newfound hantaviruses harbored by shrews, moles and insectivorous bats. Lines indicate the approximate geographic locations where reservoir hosts were captured.

Figure 2

Phylogenetic tree generated by MrBayes, using the GTR+I+Γ model of evolution, based on a 1,058-nucleotide region of the L segment of mole-, shrew- and rodent-borne hantaviruses. The phylogenetic positions of five talpid-borne hantaviruses, including Nova virus (NVA MSB95703: FJ593498), Dahonggou Creek virus (DHC DGR36708: HQ616595), Oxbow virus (OXB Ng1453: FJ593497), Asama virus (ASA N10: EU929078) and Rockport virus (RKP MSB57412: HM015221), are shown (red boxes) in relationship with hantaviruses harbored by rodents and shrews.

Figure 3

Summary of available sequences for 32 soricomorph- and chiroptera-borne hantaviruses. Of these, full-length S-segment sequences are completed for 20. None of the bat-borne hantaviruses have been fully sequenced, and specifically no full-length L-segment sequences are available. The number of nucleotides for each segment is shown for each non-rodent-borne hantavirus with the GenBank number, when available.

Figure 4

Phylogenetic trees, based on the small (S) and large (L) genomic segments, respectively, of rodent-, shrew-, mole- and bat-borne hantaviruses, generated by the maximum-likelihood and Bayesian Markov chain Monte Carlo estimation methods, under the GTR+I+ model of evolution. Because tree topologies were similar when RAxML and MrBayes were used, the trees generated by MrBayes were displayed. The numbers at each node are Bayesian posterior node probabilities (>0.7) based on 150,000 trees (left) and bootstrap values of 1,000 replicates executed on the RAxML BlackBox web server (right), respectively. The scale bars indicate nucleotide substitutions per site. The phylogenetic positions are shown for Mouyassué virus ([MOYV] JQ287716) from the banana pipistrelle, Magboi virus (MGBV] JN037851) from the hairy slit-faced bat, Longquan virus ([LQUV] JX465413-JX465422, JX465379, JX465387) from horseshoe bats and Huangpi virus ([HUPV] JX473273, JX465369) from the Japanese house bat. Representative soricomorph-borne hantaviruses include Thottapalayam virus ([TPMV] AY526097, EU001330) from the Asian house shrew, Imjin virus ([MJNV] EF641804, EF641806) from the Ussuri white-toothed shrew, Jeju virus ([JJUV] HQ663933, HQ663935) from the Asian lesser white-toothed shrew, Tanganya virus ([TGNV] EF050455, EF050454) from the Therese’s shrew, Azagny virus ([AZGV] JF276226, JF276228) from the West African pygmy shrew, Cao Bang virus ([CBNV] EF543524, EF543525) from the Chinese mole shrew, Ash River virus ([ARRV] EF650086, EF619961) from the masked shrew, Jemez Springs virus ([JMSV] FJ593499, FJ593501) from the dusky shrew, Seewis virus ([SWSV] EF636024, EF636026) from the Eurasian common shrew, Kenkeme virus ([KKMV] GQ306148, GQ306150) from the flat-skulled shrew, Qiandao Lake virus ([QDLV] GU566023, GU566021) from the stripe-backed shrew, Camp Ripley virus ([RPLV] EF540771) from the northern short-tailed shrew, Asama virus ([ASAV] EU929072, EU929078) from the Japanese shrew mole, Oxbow virus ([OXBV] FJ539166, FJ593497) from the American shrew mole, Rockport virus ([RKPV] HM015223, HM015221) from the eastern mole, and Nova virus ([NVAV] FJ539168, FJ593498) from the European common mole. Also shown are representative rodent-borne hantaviruses, including Hantaan virus ([HTNV] NC_005218, NC_005222), Soochong virus ([SOOV SOO-1] AY675349, DQ562292), Dobrava-Belgrade virus ([DOBV] NC_005233, NC_005235), Seoul virus ([SEOV] NC_005236, NC_005238), Tula virus ([TULV] NC_005227, NC_005226), Puumala virus ([PUUV] NC_005224, NC_005225), Prospect Hill virus ([PHV] Z49098, EF646763), Andes virus ([ANDV] NC_003466, NC_003468), and Sin Nombre virus ([SNV] NC_005216, NC_005217).