Retroviral integrations contribute to elevated host cancer rates during germline invasion

Gayle K. McEwen, David E. Alquezar-Planas, Anisha Dayaram, Amber Gillett, Rachael Tarlinton, Nigel Mongan, Keith J. Chappell, Joerg Henning, Milton Tan, Peter Timms, Paul R. Young, Alfred L. Roca and Alex D. Greenwood ()
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Gayle K. McEwen: Leibniz Institute for Zoo and Wildlife Research
David E. Alquezar-Planas: Leibniz Institute for Zoo and Wildlife Research
Anisha Dayaram: Leibniz Institute for Zoo and Wildlife Research
Amber Gillett: Australia Zoo Wildlife Hospital
Rachael Tarlinton: University of Nottingham
Nigel Mongan: University of Nottingham
Keith J. Chappell: University of Queensland
Joerg Henning: University of Queensland
Milton Tan: University of Illinois at Urbana–Champaign
Peter Timms: University of the Sunshine Coast
Paul R. Young: University of Queensland
Alfred L. Roca: University of Illinois at Urbana–Champaign
Alex D. Greenwood: Leibniz Institute for Zoo and Wildlife Research

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21612-7

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