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An international team of scientists analysed the ongoing colonization by two retroviruses of the germline of koalas and resulting deaths from cancer in multi-generational pedigrees of over 100 koalas in US and European Zoos. In the journal “Nature Communications”, they describe the genome sequencing of the koalas and their analysis of integration in or near genes involved in cancer, new germline integrations within a single generation, and deaths from cancer caused by the retroviral integration. Based on this work, the scientists calculated genetic risk scores (GRS) that can help guide koala breeding programs and thereby benefit koala conservation efforts.
Retroviruses integrate into the host genome when they infect cells. If this happens in the germline, the integrated viruses can be passed on from generation to generation by inheritance rather than relying on infection. This is a common process and all living organisms, including humans, have in the past incorporated retroviruses as part of their own genome. For example, the remains of retroviruses make up eight percent of the human genome. In Koalas, however, this is not an ancient process, but one that is currently unfolding – with severe health effects on Koalas living today. Koalas (Phascolarctos cinereus) are at the earliest stages of genome colonization by the Koala Retrovirus (KoRV) and suffer high cancer prevalence as a result.
The Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) in collaboration with the San Diego Zoo and Wildlife Alliance (SDZWA), zoos across Europe, the University of Nottingham and the biotechnology company Illumina have examined the genome, the life history, and the health of 111 koalas from SDZWA and European zoos representing 55 “triads” of father, mother and offspring from multiple generations to understand what happens to the koala retrovirus (KoRV) and the retrovirus “phaCin-β”, and the koala individuals over generations.
The Koala retrovirus has not been “tamed” and exhibits spread of new integrations
Bioinformatician Dr Guilherme Neumann from the Leibniz-IZW Department of Wildlife Diseases and colleagues analysed the data from the Koalas under human care. They observed that in one part of the pedigree the KoRV was integrated into a known gene that when mutated is involved in cancer. They were able to link this infection to cases where the parents and all offspring had died of cancer. In some cases, KoRV integrations in genes appeared to be beneficial to koala health, being associated with reduced cancer predisposition, greater longevity or higher reproductive output. One example is the SLC29A1 in which 50 percent of captive and wild koalas carry a KoRV insertion in an intron of this gene. Individuals with this integration showed upregulation of SLC29A1 and a lower cancer predisposition. The mechanism by which increased expression of this gene might confer protection against cancer is not yet known. Such KoRVs tended to increase in number over time – an indication that retroviral integrations can have serious consequences at early stages of genome colonisation, but become less harmful over time or even occasional have positive health effects.
The scientists also observed the spread of new integrations within a single koala generation. Some offspring had germline integrations that were not found in either parent. This means that a germline integration had occurred in the parents’ cells that produce sperm or eggs and was transmitted to their offspring while a retrovirus integration was not observed in body cells of the parents. Such rapid generation of new copies of the retrovirus in the genome demonstrates it has not been “tamed” yet like most human endogenous retroviruses – and those of many wildlife species – and still represents a health risk to koalas.
Reconstruction of retroviral integration can guide koala breeding programs
Such a large dataset with so much associated life history and health data allowed the scientists to calculate genetic risk scores (GRS). This means one could examine individual integrations and determine if they were a risk for negative outcomes, positive outcomes or had no effect on koala health at all. In one case, an animal with the highest GRS for developing leukemia associated with a KoRV that had integrated in an oncogene, died of leukemia while the project was underway emphasizing the predictive nature of the GRS.
“The GRS based on this study can help guide koala breeding programs to decrease the number of KoRVs associated with poor health prognosis while increasing those that are beneficial or have no effect in captive populations”, says Prof. Alex Greenwood, head of the Leibniz-IZW Department of Wildlife Diseases. “This could really improve captive or managed wild koala population health in the long term.” The authors of the paper in “Nature Communications” hope that with the information obtained from such a rich dataset, progress can be made in improving koala health and conservation by incorporating breeding strategies that avoid the negative health outcomes of KoRV infection while maximizing the positive effects that were also observed. Benefiting from the GRS would require the sequencing of the entire genome of the individual Koala, but in the future more cost-efficient shortcuts – e.g. primers to amplify only regions of interest in the genome or a customized SNP chip for koalas including the integrations – are potential components of a practical pipeline for zoos.
Further information on the Koala Retrovirus Project at Illumina can be found here: https://www.illumina.com/company/news-center/feature-articles/iconserve-koala-re...
Prof Dr Alex D. Greenwood
Head of the Department of Wildlife Diseases
Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW)
phone: +49(0)30 5168255
email: greenwood@izw-berlin.de
Dr Guilherme Neumann
Scientist at the Department of Wildlife Diseases
Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW)
phone: +49(0)30 5168237
email: neumann@izw-berlin.de
Neumann GB, Tarlinton R, Korkuć P, Gaffney PM, Viaud-Martinez KA, Urbaniak S, Nobuta K, Dayaram A, Mulot B, Tenes K, Alquezar-Planas DE, Roca AL, Jern P, Singleton CL, Greenwood AD (2025): Multi-generational koala pedigree analysis reveals rapid changes in heritable provirus load associated with life history traits. Nature Communications 17, 345 (2026). DOI: 10.1038/s41467-025-66312-8
Koalas (Phascolarctos cinereus)
Source: Damien Lasater
Copyright: Damien Lasater, SDZWA
Koalas (Phascolarctos cinereus)
Source: Damien Lasater
Copyright: Damien Lasater, SDZWA
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