Publikationsdatenbank

Retroviral integrations contribute to elevated host cancer rates during germline invasion (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

McEwen, Gayle K.

Alquezar-Planas, David E.

Dayaram, Anisha

Gillett, Amber

Tarlinton, Rachael

Mongan, Nigel

Chappell, Keith J.

Henning, Joerg

Tan, Milton

Timms, Peter

Young, Paul R.

Roca, Alfred L.

Greenwood, Alex D. (WE 5)

Quelle

Nature Communications

Bandzählung: 12

Heftzählung: 1

Seiten: Article number: 1316

ISSN: 2041-1723

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41467-021-21612-7

DOI: 10.1038/s41467-021-21612-7

Pubmed: 33637755

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.