From Zoo to Bedside
An Unlikely Route to Translational Research
BY JENNIFER SARGENT, NIAMS
Koalas—those docile, undeniably cute Australian marsupials—are a threatened species. Ever since the British colonization of Australia in the late 1700s, these adorable creatures have suffered immensely, and their populations have been reduced as a result of their native habitats being destroyed.
But a new, more insidious danger has emerged in the last century—a cancer-causing virus. Today, leukemia and associated lymphomas are the leading cause of death in koalas in northeastern Australia and in zoos around the world.
Surprisingly, some human-related NIH research may help to rescue the eucalyptus-munching koalas. Maribeth Eiden, chief of the Section on Directed Gene Transfer at the National Institute of Mental Health (NIMH), is developing viral-based vectors for delivering genetic material to cells in the human central nervous system (CNS). Her findings may lead to the optimization of gene-delivery vectors in humans as well as ways to prevent deadly viral attacks in koalas.
Rennett Stowe, Wikimedia Commons
NIMH scientist Maribeth Eiden is doing research that may lead to the optimization of gene-delivery vectors in humans as well as ways to prevent deadly viral attacks in koalas. Above: Koala at the Greater Los Angeles Zoo.
The deadly koala virus, discovered in 2000, is the endogenizing koala gamma-retrovirus (KoRV), which has been integrating into the koala genome over the past 100 years. KoRV is closely related to other retroviruses known to cause blood cancers such as the gibbon ape leukemia virus (GALV). KoRV is also found in healthy animals, so its association with cancers has remained enigmatic.
Eiden’s lab and a team of scientists from the Los Angeles and San Diego Zoos showed that koalas infected with the virus substrain KoRV-B had a higher incidence of malignant tumors than did noninfected koalas (Proc Natl Acad Sci U.S.A. 110:11547–11552, 2013). Based on their findings, the researchers developed an assay using the polymerase chain reaction to screen for pathogenic KoRV-B as part of an effort to prevent disease transmission among koalas (between individual animals and from mothers to their offspring).
Great news for koalas, but how does this relate to human gene therapy?
For over two decades, Eiden has been re-engineering GALV and other viruses to exploit their intrinsic properties and construct vectors for human gene therapy. She is particularly interested in the viral envelope proteins that infect cells by targeting specific host receptors. And that’s where studying koalas comes into play.
KoRV and GALV are closely related, share many of the same genes, and even use the same receptor to infect human cells. Eiden found, however, that the newly discovered pathogenic KoRV-B uses a different receptor to infect cells and that that receptor is expressed in the human CNS. She is now examining the KoRV-B envelope proteins with the goal of honing the GALV-based vectors to more specifically target the CNS.
Although Eiden and her group are primarily interested in understanding retroviruses and modifying vectors for continual improvement of human therapeutics, this collaborative project is a shining example of the impact the NIH intramural research has in unlikely places . . . even at the zoo.