Endogenous amdoparvovirus-related elements reveal insights into the biology and evolution of vertebrate parvoviruses

Abstract

Amdoparvoviruses (family Parvoviridae: genus Amdoparvovirus) infect carnivores, and are a major cause of morbidity and mortality in farmed animals. In this study, we systematically screened animal genomes to identify endogenous parvoviral elements (EPVs) disclosing a high degree of similarity to amdoparvoviruses, and investigated their genomic, phylogenetic and protein structural features. We report the first examples of full-length, amdoparvovirus-derived EPVs in the genome of the Transcaucasian mole vole (Ellobius lutescens). We also identify four EPVs in mammal and reptile genomes that are intermediate between amdoparvoviruses and their sister genus (Protoparvovirus) in terms of their phylogenetic placement and genomic features. In particular, we identify a genome-length EPV in the genome of a pit viper (Protobothrops mucrosquamatus) that is more similar to a protoparvovirus than an amdoparvovirus in terms of its phylogenetic placement and the structural features of its capsid protein (as revealed by homology modeling), yet exhibits characteristically amdoparvovirus-like genome features including: (1) a putative middle ORF gene; (2) a capsid gene that lacks a phospholipase A2 domain; (3) a genome structure consistent with an amdoparvovirus-like mechanism of capsid gene expression. Our findings indicate that amdoparvovirus host range extends to rodents, and that parvovirus lineages possessing a mixture of proto- and amdoparvovirus-like characteristics have circulated in the past. In addition, we show that EPV sequences in the mole vole and pit viper encode intact, expressible replicase genes that have potentially been co-opted or exapted in these host species.

Evolution of dependoparvoviruses across geological timescales—implications for design of AAV-based gene therapy vectors

“…Therefore, it is feasible that similar mechanisms could be a factor affecting the role of AAV–EVE integrations, providing possible explanations for the conservation of dependoparval-EVEs through multiple speciation events within these lineages. For example, in the case of an EVE of amdoparvovirus origin identified within the Transcaucasian mole vole ( Ellobius lutescens ) genome, an intact NS gene fused with a bZIP transcription factor’s ORF ( Pénzes et al. 2018 ).…”

“…EVEs can be derived from a variety of diverse viral families with RNA genomes, like retroviruses, or DNA genomes such as the Parvoviridae , which is composed of various genera including Ambidensovirus , Protoparvovirus , Amdoparvovirus , and Dependoparvovirus ( Belyi, Levine, and Skalka 2010 ; Katzourakis and Gifford 2010 ; Arriagada and Gifford 2014 ; Smith et al. 2016 ; Pénzes et al. 2018 ).…”

An ancient lineage of highly divergent parvoviruses infects both vertebrate and invertebrate hosts

“…Sequences derived from parvoviruses occur relatively frequently in animal genomes (13, 14, 17, 25, 26). However, these sequences overwhelmingly derive from a small proportion of parvovirus lineages.…”

“…However, these sequences overwhelmingly derive from a small proportion of parvovirus lineages. For example, ambidensovirus-derived EPVs dominate invertebrate genomes (14), whereas vertebrate EPVs almost exclusively derive from dependoparvoviruses, protoparvoviruses, or viruses closely related to these two genera (12, 13, 25, 26). In this study we found no trace of ChPV-derived sequences in tetrapod genomes, despite recent evidence that ChPVs infect this host group (21).…”

Ecology and Infection Dynamics of Multi-Host Amdoparvoviral and Protoparvoviral Carnivore Pathogens

“…Amdoparvovirus and Protoparvovirus are monophyletic and both include viruses capable of infecting a wide range of carnivore hosts that, in some cases, overlap. However, they are separated by important genetic differences and the mechanisms behind "host-non-specificity" differ considerably between the two [18,37,65]. We may, therefore, expect significant differences in viral ecology and cross-species transmission dynamics for these two groups.…”