
Cora Singleton, DVM, Dipl. ACZM, explains how scientists dive deep into the DNA of generations of San Diego Zoo koalas to expand our understanding of koala retrovirus.
Koala retrovirus (KoRV) is potentially a significant threat to koalas in the wild and in human care. Retroviruses are interesting because they insert (integrate) into the host cell’s genome as part of their life cycle. Retroviruses exist in both exogenous and endogenous forms. Exogenous viruses can be spread from one person or animal to another, where they can cause disease by infecting the somatic cells (body cells) and use the host’s cell machinery to make more virus. Endogenous viruses are a special category of viruses that have infected the germ cells (egg or sperm) at some point in the past. By infecting germ cells, the integrated virus DNA in the host genome is transferred from one generation to the next, becoming a permanent part of the host’s genome in all cells of the body. Many endogenous viruses can no longer replicate independently or cause active viral infections. Most endogenous viruses are very old and are considered “fossils” of past viral infections. However, endogenous koala retroviruses have integrated into koala DNA only recently, evolutionarily speaking. The location in the host DNA where the KoRV integrates is important, as it leads to disruption of host gene function and predisposes koalas to certain diseases.
The prevalence of KoRV varies across populations. In the more northern Australian states of Queensland and New South Wales, the prevalence of infection is 100 percent, whereas in the southern states of Victoria and South Australia, the prevalence of infection can be as low as 30 per-cent. All koalas living in North American zoos have endogenous KoRV because the founder koalas came from Queensland in the late 1970s and early 1980s.

Koala retrovirus (KoRV) is potentially a significant threat to koalas in the wild and in human care.
Infection with KoRV is putatively associated with certain diseases in koalas. Cancers such as lymphoma and leukemia, as well as other bone marrow cancers and tumors of the bone, affect koalas in the wild and in human care. Also, KoRV infection may alter immune function, which may predispose koalas to other infectious diseases such as a fungal infection called cryptococcosis, and a bacterial infection called chlamydiosis, which causes widespread infertility in koalas in Australia, threatening already stressed koala populations facing drought, bush fires, and habitat loss.
The North American koala population consists of 50 koalas living at 9 different zoos. With 30 resident koalas, the San Diego Zoo cares for the largest colony of koalas outside of Australia and advises on the co-operative care of this iconic and specialized marsupial in North America. With decades of documented pedigrees, extensive health and husbandry data, and a large bank of biological samples, the North American koala population is viewed as extremely valuable for helping understand the biology and epidemiology of KoRV infection.

Using whole genome sequencing of 91 living and deceased koalas, the research team is investigating where KoRV integrates into the koala genome, how these integration sites are generated and inherited, and how the integration patterns are related to health outcomes.
Molecular and genomic technologies are needed to study KoRV, but their application on a large scale has not been accessible until now. San Diego Zoo Wildlife Alliance has partnered with Illumina, a leading genomic sequencing technology company, and an international team of koala and KoRV experts at Leibniz Institute for Zoo and Wildlife Research, The University of Sydney, the Australian Museum, and the University of Nottingham. Using whole genome sequencing of 91 living and deceased koalas, the research team is investigating where KoRV integrates into the koala genome, how these integration sites are generated and inherited, and how the integration patterns are related to health outcomes.
This partnership helps us clear a major technical hurdle in characterizing individual, familial, and population KoRV profiles, and will create the largest koala pedigree genomic database to date. Understanding how KoRV acts in the genome and how the North American koala population compares with Australian regional populations can help us make conservation management decisions (breeding, importation, translocation) that limit disease and optimize the health of koalas in their native range and under human care. This effort exemplifies how zoo populations can con-tribute meaningfully and directly to under-standing and mitigating disease threats to koala conservation.