For decades, chimpanzees have been the primary animal model for studying hepatitis C virus (HCV) infection. Efforts to develop other animal models have so far failed because chimps are the only species other than humans that are naturally susceptible to HCV. But as regulations surrounding chimpanzee research in the US have become more restrictive, the need for alternative models to test potential drugs and vaccines against HCV has become more urgent. Now, two independent research groups report advances in the development of new animal models for studying HCV, one rodent and the other primate.

While at The Rockefeller University (New York, NY), Alexander Ploss began developing a mouse model of HCV infection by engineering mice to express two proteins found on the outside of human liver cells, CD81 and occludin. This enabled the virus to infect the animals but not to replicate well. So Ploss's team took it a step further, breeding the liver-protein-expressing mice with another mouse line engineered to have a defect in antiviral response. The offspring of this cross are susceptible to entry and replication of HCV (Nature published online 31 July 2013; doi:10.1038/nature12427). The team hopes that the mice will prove useful for studying the HCV infection cycle in vivo, testing candidate drugs and evaluating vaccine efficacy. “It has been very difficult to get to this point,” Ploss told Nature News. Although “this model still cannot replace chimpanzees,” he said, “it gives us a first glimpse of what may be possible with mice in coming years.”

Meanwhile, across town at Icahn School of Medicine at Mount Sinai (New York, NY), Matthew Evans and Valerie Gouon-Evans were working to create a more closely related model for HCV infection in pigtail macaques (Macaca nemestrina). Liver cells that had been differentiated from macaque stem cells supported the HCV life cycle in vitro, although HCV infection efficiency was lower than in human liver cells. By modifying either of the same two liver proteins that Ploss's team altered in mice, CD81 and occludin, Evans' group increased HCV infection efficiency of the macaque cells (Gastroenterol. published online 26 July 2013; doi:10.1053/j.gastro.2013.07.026). If in vivo experiments are successful, the research may lead to the validation of the pigtail macaque as a model for HCV studies and vaccine development. “These findings may open doors for the field of HCV research, lead to new animal models, and hopefully vaccines and therapies,” Evans said in a press release.