Diversification of mammalian deltaviruses by host shifting

Laura M Bergner,Richard J Orton,Alice Broos,Carlos Tello,Daniel J Becker,Jorge E Carrera,Arvind H Patel,Roman Biek,Daniel G Streicker

doi:10.1073/pnas.2019907118

Abstract

Hepatitis delta virus (HDV) is an unusual RNA agent that replicates using host machinery but exploits hepatitis B virus (HBV) to mobilize its spread within and between hosts. In doing so, HDV enhances the virulence of HBV. How this seemingly improbable hyperparasitic lifestyle emerged is unknown, but it underpins the likelihood that HDV and related deltaviruses may alter other host-virus interactions. Here, we show that deltaviruses diversify by transmitting between mammalian species. Among 96,695 RNA sequence datasets, deltaviruses infected bats, rodents, and an artiodactyl from the Americas but were absent from geographically overrepresented Old World representatives of each mammalian order, suggesting a relatively recent diversification within the Americas. Consistent with diversification by host shifting, both bat and rodent-infecting deltaviruses were paraphyletic, and coevolutionary modeling rejected cospeciation with mammalian hosts. In addition, a 2-y field study showed common vampire bats in Peru were infected by two divergent deltaviruses, indicating multiple introductions to a single host species. One vampire bat-associated deltavirus was detected in the saliva of up to 35% of individuals, formed phylogeographically compartmentalized clades, and infected a sympatric bat, illustrating horizontal transmission within and between species on ecological timescales. Consistent absence of HBV-like viruses in two deltavirus-infected bat species indicated acquisitions of novel viral associations during the divergence of bat and human-infecting deltaviruses. Our analyses support an American zoonotic origin of HDV and reveal prospects for future cross-species emergence of deltaviruses. Given their peculiar life history, deltavirus host shifts will have different constraints and disease outcomes compared to ordinary animal pathogens.

Highlights

Efforts to distinguish competing evolutionary hypotheses for deltaviruses have been precluded by the remarkably sparse distribution of currently-known Hepatitis delta virus (HDV)-like agents across the animal tree of life
Unlike conventional pathogens, the obligatory dependence of deltaviruses on evolutionarily independent helpers creates a barrier to cross-species transmission that might be expected to promote host specificity
Deltavirus host shifts could conceivably arise through several processes

Summary

Introduction

Efforts to distinguish competing evolutionary hypotheses for deltaviruses have been precluded by the remarkably sparse distribution of currently-known HDV-like agents across the animal tree of life. Single representatives are reported from arthropods (Subterranean termite, Schedorhinotermes intermedius), fish (a pooled sample from multiple species), birds (a pooled sample from 3 duck species, Anas gracilis, A. castanea, A. superciliosa), reptiles (Common boa, Boa constrictor) and mammals (Tome’s spiny rat, Proechimys semispinosus), and only two are known from amphibians (Asiatic toad, Bufo gargarizans; Chinese fire belly newt, Cynops orientalis) (4-7). Most share minimal homology with HDV, even at the protein level (< 25%), frustrating robust phylogenetic re-constructions of evolutionary histories (see SI Appendix, Fig. S1). The distribution of deltaviruses may reflect rare host shifting events among divergent taxa. Additional taxa could reveal ancient co-speciation of HDV-like agents with their hosts or evidence for host shifting

Methods

Results

Conclusion