Researchers from the Icahn School of Medicine at Mount Sinai in New York may have created a new animal model for the study of the hepatitis C virus (HCV)—pigtail macaques. Macaques live in Africa and Asia, and are closely related to humans and chimpanzees. For decades investigators who have been trying unsuccessfully to develop new animal models, other than humans and chimpanzees. The team of researchers led by Matthew Evans, PhD, and Valerie Gouon-Evans, PhD, discovered that by differentiating stem cells into liver cells, they could infect pigtail macaques with HCV. These findings represent a significant breakthrough.
First, Gouon-Evans, an Assistant Professor in the Department of Developmental and Regenerative Biology at Mount Sinai, collaborated with a team at the Fred Hutchison Cancer Research Center in Seattle to convert macaque stem cells into liver cells. Next, Evans, an Assistant Professor in the Department of Microbiology at Mount Sinai, and his team attempted to infect these cells with HCV in a petri dish. They observed that these differentiated cells were able to support HCV infection and replication, but not as effectively as in human liver cells.
"Now that we know that HCV infection in macaque cells is possible, we wanted to find out why it only worked in liver cells that were derived from stem cells," says Gouon-Evans. "By identifying where in the viral life cycle the infection is dysfunctional, we can develop an effective animal model of HCV."
Investigators found the cause--changes in a cell surface receptor in the macaques. This obstacle was overcome by genetically introducing the human version of this receptor in macaque cells.
Next, the Mount Sinai team will infect macaques with the altered HCV. Through genetic manipulation, this modified HCV will encounter more functional receptors, allowing for more efficient replication.
“Our discovery shows that by manipulating either host or viral genetics we can efficiently infect macaque cells,” said Evans. “These findings may open doors for the field of HCV research, lead to new animal models, and hopefully vaccines and therapies.”
The study, “Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection,” was published online July 26, 2013, in the journal Gastroenterology.
Source: Mount Sinai press release dated July 26, 2013