Exogenous amdoparvoviruses (Parvoviridae) in arvicoline voles: the molecular evolution and ecology of a novel host-viral association

Amdoparvoviruses are best known as agents of disease in carnivorans, but here we provide the first in-depth molecular evolutionary and ecological information for an amdoparvovirus in wild rodents (field voles, Microtus agrestis). We applied an RNA-sequencing approach in lung tissue that yielded high diagnostic sensitivity and multiple full or near-full coding sequences for the new virus (field vole amdoparvovirus, FVAV) in individual voles. FVAV is most similar to amdoparvoviruses in European foxes and wildcats. We present evidence that FVAV is an exogenous, endemic, high-prevalence infection with a short-term history of horizontal transmission and recombination within voles and arising from an ancestral background of dynamic host usage and inter-lineage recombination. FVAV molecular structures involved in host exploitation share a highly conserved functional and evolutionary pattern with those in other amdoparvoviruses. The more variable regions within these structures evolve principally by apparently neutral processes and FVAV within-population mutation distribution mirrors that across the Amdoparvovirus phylogeny. Nonetheless, we did find some evidence of adaptive selection in the most variable regions and we also found convergent host-specific features in the modelled capsid protein of divergent arvicoline-associated lineages that might tend to restrict host range and support that FVAV is a vole-specialist. Increasing FVAV expression was associated with pulmonary inflammation and suppressed splenic T-cell activation, consistent with a potential to drive disease processes as in other amdoparvoviruses. Importantly, our approach highlights the de novo sequence assembly of viral RNA products from shotgun sequencing of rRNA-depleted RNA from tropic tissues in individual hosts as a sensitive and robust means of detecting and characterising not only RNA viruses but also DNA viruses.