The role of koala retrovirus integrations in promoting neoplasia in koalas (Phascolarctos cinereus). In Proceedings of the Second Koala Retrovirus Workshop, ed. D. E. Alquezar-Planas, D. P. Higgins, C. L. Singleton, and A. D. Greenwood

Abstract

Koalas suffer unusually high rates of neoplasia. There has been a long-standing correlation between koalas with the koala retrovirus (KoRV) and development of neoplasia which has lacked a mechanistic explanation. We describe recent results that demonstrate that many KoRV integrations lead to neoplasia by (I) inserting into somatic cells preferentially near oncogenes, (II) inserting into germ cells near oncogenes predisposing koalas to cancer, and (III) transduction—replacing KoRV genes with oncogenes, resulting in drastic upregulation of the transduced gene. The high mortality associated with integration-driven promotion of neoplasia may explain the increased prevalence of dysfunctional recombinant KoRVs (recKoRVs), which, over time, could replace KoRV, thereby slowing the production of novel detrimental integration sites.