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- Title
Expression and high levels of insertional polymorphism of an endogenous gammaretrovirus lineage in dogs.
- Authors
Jarosz, Abigail S.; Pendleton, Amanda L.; Lashbrook, Michael J.; Cech, Erica; Altieri, Madison; Kunch, Austin; Modiano, Jaime F.; Halo, Julia V.
- Abstract
Despite the absence of a confirmed exogenously replicating retrovirus in Canis lupus familiaris (C. familiaris), past retroviral infections are evident in the genomes of living animals via the presence of endogenous retroviruses (ERVs). Although gammaretrovirus-like transcripts and enzyme activities were previously reported to be present in canine leukemias and lymphomas, those findings were not further explored. Initial analysis of the C. familiaris reference genome revealed a minor subset of one ERV lineage, classified as CfERV-Fc1(a), or Fc1(a) here, with features characteristic of recent integration, including the presence of ORFs and identical or nearly identical LTRs. Our previous analysis of whole genome sequence data belonging to extant Canidae revealed a burst of past infections in Canis ancestors resulting in numerous young, polymorphic, and highly intact loci now segregating in dogs. Here, we demonstrate the expression of full-length Fc1(a) proviruses in tissues collected from healthy animals and from animals with cancer. We observed significantly higher expression in samples of dogs with various cancer diagnoses when compared to samples from healthy dogs. Genotyping of insertionally polymorphic Fc1(a) loci identified candidate expressed proviruses and delineated distributions over sample groups. Collectively, the data show that Fc1(a) proviruses retain biological activity in the domestic dog and provides a means to examine potential genetic links with disease states in this species. Author summary: The domestic dog is an important biomedical model of human genetics and disease. Until now, the dog has been largely excluded from research focusing on retrovirus biology and retrovirus-host coevolution in the context of the canine as a host. Our work reveals that numerous recently integrated endogenous retroviruses are variably present in the genomes of domestic dogs including ones that are transcriptionally active or are present within or near genes, and that transcriptional activity is significantly elevated in tumors of various canine cancers. Thus, our work characterizes a previously unexplored resource of genomic impact to the domestic dog as a model of health and disease. The results from this study begin span a significant knowledge gap in our understanding of retrovirus-host dynamics in the dog as a biomedical model of genetics and improve our understanding of the biological activity and prevalence of a zoonotic-relevant and highly intact endogenous retrovirus lineage in the domestic dog.
- Subjects
DOGS; RETROVIRUS diseases; CANIDAE; WHOLE genome sequencing; ENDOGENOUS retroviruses; CANIS; GENETICS
- Publication
PLoS Genetics, 2023, Vol 19, Issue 12, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1011083