Groundhogs Saving Humans & Chimps

Drug Discovery and Development
April 1, 2004
Some Model Organisms Are Mightier Than the Mouse
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Chronic hepatitis B virus (HBV) is one of the 10 most common causes of death. Worldwide, more than one million out of the 350 million chronic carriers of HBV die each year from complications of the disease. In the United States, approximately 1.25 million people are believed to have chronic HBV and an estimated 200,000 people become newly infected each year.

Approximately 4,000 to 5,000 people in the United States die each year from hepatitis-B-related chronic liver disease or liver cancer, and it is the leading cause of liver cancer. Endeavors to contain the global pandemic of human HBV infection have been hindered by the virus's limited host range and the inability to propagate HBV in cell culture. Then, in waddles the woodchuck (Marmota monax), more commonly known as the groundhog.

Woodchuck hepatitis virus (WHV) is closely related to HBV in its virus genetic organization and mechanism of replication. "The groundhog, the one who just saw his shadow, has its own hepatitis virus that develops into a progressive hepatitis and hepatocellular carcinoma that's very similar to the HBV-associated hepatocellular carcinomas in humans," says Leland. The predictable course of experimental WHV infection leading to liver disease in woodchucks makes them an ideal animal model in which to study the natural history of hepadenavirus and to develop effective antiviral strategies.

Research comparing the results of the effect of nucleoside analogs in woodchucks with their effect in humans demonstrates that it is an excellent model to test anti-HBV therapies. Studies show that without any treatment, more than 75% of infected woodchucks die by age 3 years, usually from primary liver cancer due to WHV. By age 4, more than 95% die due to WHV-related primary liver cancer, a sequela that is common in humans with HBV. "It's a reproducible model, found in the wild, with a much shorter time course and many similarities to the human disease," says Leland.

Historically, chimpanzees have been the cornerstone of all research on HBV infectivity, safety, and vaccine efficacy. The woodchuck model has a major advantage in that it can be adapted to the experimental laboratory and therefore eliminate many of the ethical and endangered status concerns associated with using chimpanzees.