Cross-Species Transmission in the Speciation of the Currently Known Murinae-Associated Hantaviruses

Abstract

To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried by Niviventer confucianus and other Murinae-associated hantaviruses, genome sequences of novel variants of DBSV were recovered from Niviventer rats trapped in the mountainous areas of Wenzhou, China. Genetic analyses show that all known genetic variants of DBSV, including the ones identified in this study, are distinct from other Murinae-associated hantaviruses. DBSV variants show geographic clustering and high intraspecies diversity. The data suggest that DBSV is a distinct species in the genus Hantavirus. Interestingly, DBSV shows the highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the sequences of the N, GPC, and L proteins, while N. confucianus is more closely related to Rattus norvegicus New emerging viral pathogens, e.g., avian and swine influenza viruses (28, 41), severe acute respiratory syndrome (SARS) coronavirus (17), and human immunodeficiency virus (16, 51), cause epidemics (or pandemics) in humans by changing or expanding their host range. These pathogens are a considerable threat to human and/or wildlife health, agricultural production, and public security (5, 36). Almost all of the novel viruses have circulated in their reservoir hosts for a long time before emerging in humans or other animals (11,36,37). Zoonotic viral pathogens such as hantaviruses and rabies virus show high genetic diversity that depends on natural hosts or geographic origins (7,22,43). The role of cross-species transmission in the generation of a new virus species should be studied in greater detail (26), and better understanding of the evolutionary relationship between zoonotic pathogens and their hosts may help in the prevention and control of (re)emerging diseases.The hantavirus genome consists of three RNA segments, i.e., small (S), medium (M), and large (L) segments; they encode, respectively, the nucleocapsid (N) protein (in some hantaviruses, the nonstructural NSs protein), the glycoprotein precursor (GPC) of the two envelope glycoproteins (Gn and Gc), and the viral RNA-dependent RNA polymerase (RdRP) (the L protein) (44). At least 23 established and 30 tentative hantavirus species have been identified worldwide in rodents and insectivores (42). Identification of insectivore-carried hantaviruses has increased especially rapidly during the last 5 years (22,24). Each species of these known hantaviruses is specifically associated with one or several closely related rodent or insectivore hosts (42). As the phylogeny of hantaviruses may be congruent with their hosts, hantaviruses are considered to have coevolved (cospeciated) with their respective rodent or insectivore hosts (20,21,23,25,38,39,43,44,52). Recently, Ramsden et al. proposed that there was no codivergence between hantaviruses and their hosts and that the similarities between the phylogenies of hantaviruses and their hosts are the result of a more recent history of preferential host switching and local adaptation (46). Further studies are needed to determine i...

Reconstructing the evolutionary origins and phylogeography of hantaviruses

“…Specifically, closely related hantaviruses are generally found in closely related hosts as opposed to more distant hosts. Topological congruence in divergence patterns between hantaviruses and their hosts is widespread throughout hantavirus evolutionary history, and in particular hantavirus lineages is significantly supported over other patterns, such as host-switching [13,31,58]. Overall, hantavirus diversification is highly structured by host identity at the host subfamily, family, and order levels {Bayesian tip-association significance testing (BaTS) program statistics, association index (AI), and Fitch parsimony statistic (PS) P = 0 indicate that the probability of the observed degree of phylogenetic correlation or structure in the data occurring by chance is zero [59]}.…”

“…In most cases, the evolutionary history of a group is calibrated against a fossil record or using specimens drawn from different times. Several virus evolutionary histories have been calibrated the latter way, from viruses sampled over time [38,58,62–65], with best results when the span of sampling is of a scale with the evolutionary history and when rates are relatively consistent through time and across lineages. Tip-dated methods have given variable estimates of the rate of evolution of hantaviruses depending on the lineage, on the order of 10 −2 to 10 −4 substitutions per site per year [38,58,62,65].…”

“…Several virus evolutionary histories have been calibrated the latter way, from viruses sampled over time [38,58,62–65], with best results when the span of sampling is of a scale with the evolutionary history and when rates are relatively consistent through time and across lineages. Tip-dated methods have given variable estimates of the rate of evolution of hantaviruses depending on the lineage, on the order of 10 −2 to 10 −4 substitutions per site per year [38,58,62,65]. Direct measurements of evolutionary rates in specific hantaviruses currently circulating in nature have been reported on the order of 10 −3 substitutions per site per year [66,67].…”

“…At the same time, positive selection has presumably played a role in shaping hantavirus diversity, although the data are limited and the precise mechanisms are still unknown. Lin and colleagues [58] report non-significant phylogenetic signals for positive selection in S and M segments for particular internal branches at clade-defining sites within the Murinae-borne hantavirus lineage. However, Razzauti and coworkers [71] suggest that particular ‘preferred’ genotypes of PUUV may persist over time, based on a 5 year study of bank voles from Finland.…”

Heligmosomoides neopolygyrus Asakawa & Ohbayashi, 1986, a cryptic Asian nematode infecting the striped field mouse Apodemus agrarius in Central Europe

“…Although there are reports of fossil A. agrarius from southern France from 17 000 years BP [40], it is generally thought that the species was extinct in Europe following the last ice age, and that it has recolonised central Europe within the last few thousand years [41][42][43]. The earliest fossils in Poland date to c. 1000 years BP [42], and dating of hantavirus divergence suggests that the species acquired Saarema virus from A. flavicollis no more than 1000 years ago [41]. The recent importation of other pathogens into western Europe with this host has also been noted; Hildebrand et al [44] record a range of unusual Bartonella genotypes in A. agrarius, including some most closely related to Far Eastern isolates.…”