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Published VersionCC BY V4.0, Open Access
Journal article
Retroviral integrations contribute to elevated host cancer rates during germline invasion
Nature Communications, Vol.12(1), pp.1-13
2021
PMID: 33637755
Abstract
Repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala (Phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by high cancer prevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.
Details
- Title
- Retroviral integrations contribute to elevated host cancer rates during germline invasion
- Authors
- Gayle K McEwen (Author) - Leibniz Institute for Zoo and Wildlife ResearchDavid E Alquezar-Planas (Author) - Leibniz Institute for Zoo and Wildlife ResearchAnisha Dayaram (Author) - Leibniz Institute for Zoo and Wildlife ResearchAmber Gillett (Author) - Australia Zoo Wildlife Hospital, Beerwah, QLD, AustraliaRachael Tarlinton (Author) - University of NottinghamNigel Mongan (Author) - University of NottinghamKeith J Chappell (Author) - The University of QueenslandJoerg Henning (Author) - The University of QueenslandMilton Tan (Author) - University of Illinois at Urbana ChampaignPeter Timms (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyPaul R Young (Author) - The University of QueenslandAlfred L Roca (Author) - University of Illinois at Urbana ChampaignAlex D Greenwood (Corresponding Author) - Freie Universität Berlin
- Publication details
- Nature Communications, Vol.12(1), pp.1-13
- Publisher
- Nature Publishing Group
- Date published
- 2021
- DOI
- 10.1038/s41467-021-21612-7
- ISSN
- 2041-1723
- PMID
- 33637755
- Copyright note
- Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Organisation Unit
- University of the Sunshine Coast, Queensland; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99510405402621
- Output Type
- Journal article
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