Researchers have uncovered a method to mimic the hepatitis C in rodents. In work published in Science, the team of researchers describes how they discovered a virus that is closely related to hepatitis C, but is able to infect rats and mice. The researchers found that this new animal model recapitulates much of the human disease, a breakthrough that should accelerate hepatitis C vaccine research.
Researchers around the world rely heavily on animal models to study human disease. "We need to use animals to watch the disease develop over time and monitor how the immune system responds," explains lead author on the new research. "This hasn't been feasible for the hepatitis C virus, which has made our work very difficult."
The problem is that hepatitis C is a highly specific virus, infecting only humans and chimpanzees. This means that researchers must rely on blood samples and liver biopsies from infected patients to study the disease. These limited and infrequent samples provide only partial information about how the disease progresses and make it difficult to test new vaccines.
In 2014, however, there was an unexpected breakthrough. While studying the pathogens that infect common rats on the streets of New York City, Ian Lipkin, a professor at Columbia University, discovered a rodent hepacivirus that belongs to the same family of viruses as hepatitis C. Lipkin and his colleague Amit Kapoor quickly shared the virus with the Rice lab, hoping that it would enable them to create a rodent version of the disease.
Mice are the preferred animal model for much of modern biological research, with a host of genetic tools and techniques that make mechanistic studies possible. The researchers set out to explore whether the rat virus could also infect mice. They isolated the hepacivirus from rats and exposed standard laboratory mice to the disease. The experiment worked: the mice developed a hepacivirus infection that mimicked many of the features of human hepatitis C.
There was one notable difference, however. "In human patients, hepatitis C virus infection has two outcomes," author explains. "Initially, it is acute, and a small percentage of patients fully recover from infection. However, most people progress to a chronic form of the disease that will continue to affect them unless they are treated." The team found that mice with a healthy immune system experience the acute form of the disease and then recover, while immune-compromised animals become chronically infected and remain so even after their immune systems are restored.
The researchers are now using their new animal models to gain insight into how hepatitis C infection progresses, and to understand how the body reacts. "This research will help unravel mechanisms of liver infection, virus clearance, and disease mechanisms," senior author says, " which should prove valuable as we work to develop and test hepatitis C vaccines that can help to finally eradicate the disease around the world."