Apr. 11 2013

Newly discovered mouse viruses could pave the way for future progress in hepatitis C research, finally enabling scientists to study the human disease and vaccines in an animal model. In a study published in mBio, the journal of the American Society for Microbiology, scientists at the Center for Infection and Immunity (CII) at Columbia's Mailman School of Public Health describe their search for viruses related to the human hepatitis C virus (HCV) and human pegiviruses (HPgV) in frozen stocks of wild mice. The discovery of several new species of hepaciviruses and pegiviruses that are closely related to human viruses suggests they might be used to study these diseases and potential vaccines in mice, without the need for human volunteers.

About 2% of the population is infected with the hepatitis C virus and 5% is infected with human pegiviruses, but it's been difficult to study new drugs or develop vaccines against these infections because the human strains do not infect animals that can be studied in the lab. Lead author Amit Kapoor, PhD, assistant professor, says it surprised him to find similar viruses in mice.

"People have been waiting for decades to find something like this. It was shocking for me to see that the viruses are there and there are so many of them," says Dr. Kapoor.

The scientists screened an archive of more than 400 frozen rodents, mostly deer mice, for viruses related to the human hepatitis C virus and human pegiviruses. The search turned up a number of candidates, and they selected two for complete genome sequencing: a rodent hepacivirus (RHV) found in deer mice and a rodent pegivirus (RPgV) found in a white-throated woodrat. Sequencing confirmed that the viruses are very closely related to human strains but they represent several novel species in the Hepacivirus and Pegivirus genera within the family Flaviviridae.

These rodent viruses have genes, proteins, and translational elements that closely mirror those found in human hepaciviruses and pegiviruses, suggesting they have great potential for use in the lab. Animal models of hepatitis would help scientists explore the ways these viruses causes disease and aid in the design of treatments and vaccines. Human pegiviruses, on the other hand, have unknown effects, so studying how they work in rodents could well point the way to what they might do in the human body and why so many people are infected.

The researchers also found instances of a single animal infected with multiple hepaciviruses. Such co-infections have also been observed with HCV in humans, suggesting that the immune response to HCV is different than with most viral infections—a finding that has implications for vaccine design. "It also supports the potential use of rodent hepaciviruses in developing models for human disease," says W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the CII.

The lab at the Center for Infection and Immunity is now focused on exploring the biology of these viruses. "We are trying to infect deer mice, to study biological properties of these hepatitis C-like viruses," says Dr. Kapoor. "And if we find one of these viruses is hepatotrophic [having an attraction to the liver] and causes disease similar to hepatitis C, that would be a big step forward in understanding hepatitis C-induced pathology in humans."