Researchers discover new retroviruses in polar bear Knut and panda Bao Bao

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Following the death of the polar bear Knut at Berlin Zoo, examinations carried out at the Leibniz Institute for Zoo and Wildlife Research in Berlin showed that Knut was suffering from virus-induced encephalitis (acute inflammation of the brain). Researchers at Saarland University and IZW have now analysed his genetic material and discovered and characterised new sequences of endogenous retroviruses. The retroviruses were also found in another former resident of Berlin Zoo: the giant panda Bao Bao. The work of the research team indicates that these viruses were inserted into the genome of an ancestor of both bear species some 45 million years ago. These newly discovered viruses are very similar to those found in the genetic material of bats, cattle and even humans. Some of these viruses are suspected of being involved in triggering some diseases in humans. The study has now been published in a recent edition of the journal Virology.

Endogenous retroviruses (ERVs) are viruses that at some point in the past inserted themselves into the nuclear genome of a host's germ cell. Once integrated in a germ cell the virus would be passed on from one generation to the next and the endogenous retroviral genome would therefore be inherited to new species that evolve from the original host. 'ERV sequences and fragments make up about eight per cent of the human genome,' explains Professor Jens Mayer from the Department of Human Genetics at Saarland University. Endogenous retroviruses are found not only in humans, but also in other mammals such as horses, cattle, apes, koalas and, as has now been shown, in polar bears and giant pandas.

Working in collaboration with Professor Alex D Greenwood and Kyriakos Tsangaras from the Leibniz Institute for Zoo and Wildlife Research in Berlin, Jens Mayer has been taking a closer look at the DNA sequences from polar bears and great pandas. 'We have characterised endogenous retroviral sequences in both bear species and found a strong similarity between the two, which indicates that these two virus species are closely related,' says human geneticist Mayer. The researchers also identified ERV sequences in other bear species such as the brown bear, the black bear and the spectacled bear. 'Using molecular dating methods we have now been able to show that the retrovirus became integrated into the genetic material of an ancestor of today's bear species around 45 million years ago,' explains Greenwood. The research team also showed that the original retrovirus was closely related to those found in the genomes of bats and cattle. Interestingly, the viruses found in bears exhibit strong similarity with several endogenous retroviruses found in the human genome. 'Some of these sequences are suspected of playing a role in the occurrence of cancer, neurodegenerative or autoimmune diseases,' says Mayer.

The sort of extensive genome analysis of different species of wildlife carried out in this study helps scientists gain a better insight into the evolution of retroviruses by learning which retroviruses infected which groups of animals millions of years ago. The data can also provide valuable information on the evolutionary development of mammals. The researchers make use of a variety of techniques to analyse DNA sequences, including very recent high-throughput ('next generation') sequencing methods that facilitate highly efficient DNA sequencing.

### In addition to research scientists from Saarland University and the Leibniz Institute for Zoo and Wildlife Research, scientists from the following institutions were also involved in the study: the Berlin Center for Genomics in Biodiversity Research, the Natural History Museum of Denmark, the Department of Biochemistry and Biophysics at the University of California (San Francisco), the Berlin Institute for Medical Systems Biology and the Institute of Virology at Freie Universität Berlin.

Background information: Professor Dr Jens Mayer carries out research in the Department of Human Genetics at the Center for Human and Molecular Biology, Saarland University. The main focus of his research work is human endogenous retroviruses (HERVs). Questions that Mayer is interested in include how these viruses have altered our genome, how they influence the functions of our genetic material and in which diseases HERVs may play a role. His expertise in analysing the human genome, particularly HERV sequences, can assist studies such as the present one that analyse the genomes of other species, particularly their endogenous retroviruses.

Professor Alex D Greenwood is head of the Department for Wildlife Diseases at the Leibniz Institute for Zoo and Wildlife Research (IZW) and holds the Chair for Wildlife Diseases at the Faculty of Veterinary Medicine at Freie Universität Berlin. An important focus of the research in the department is reciprocal pathogen transmission between wild and domesticated animals, including the transmission of pathogens in zoo animals. The research work uses modern methods of veterinary medicine, molecular medicine and electron microscopy.

Publication: Mayer J, Tsangaras K, Heeger F, Avila-Arcos M, Stenglein MD, Chen W, Sun W, Mazzoni CJ, Osterrieder N, Greenwood AD (2013): A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca). Virology 443, 1-10. doi: 10.1016/j.virol.2013.05.008.

Link to publication: http://www.sciencedirect.com/science/article/pii/S0042682213002675

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Questions can be addressed to:

Professor Jens Mayer PhD
Department of Human Genetics
Center for Human and Molecular Biology
Saarland University
Tel.: +49 (0)6841 16-26627
E-mail: jens.mayer(at)uks.eu

Professor Alex D Greenwood PhD
Department for Wildlife Diseases
Leibniz Institute for Zoo and Wildlife Research (IZW)
Tel.: +49 (0)30 5168-255
E-mail: greenwood(at)izw-berlin.de

Steven Seet
Public Relations
Leibniz Institute for Zoo and Wildlife Research (IZW)
Tel.: +49 (0)30 5168-125
E-mail: seet(at)izw-berlin.de