For the first time Icahn School of Medicine researchers have
identified that the hepatitis C virus can replicate in monkeys. The new
findings may lead to the first new animal model and provide new avenues
for developing treatments and vaccines for this disease, which impacts
more than three million people in the United States.Scientists have tried for decades to develop animal models to
study HCV, but the virus was incapable of infecting any species except
for humans and chimpanzees. With a recent National Institutes of
Health-imposed moratorium restricting chimpanzee research, the Mount
Sinai research team turned to a close relative of chimpanzees and
humans—macaques. Led by Matthew Evans, PhD, and Valerie Gouon-Evans,
PhD, of Mount Sinai, the research team sought to find out why previous
attempts to infect macaques with HCV failed. Dr. Gouon-Evans, who is Assistant Professor of in the Department of
Developmental and Regenerative Biology at Mount Sinai, worked with a
team at the Fred Hutchison Cancer Research Center in Seattle to
differentiate macaque stem cells into liver cells. Dr. Evans, who is an
Assistant Professor in the Department of Microbiology, and his team then
attempted to infect these cells with HCV in a petri dish. They found
that these differentiated cells were able to support HCV infection and
replication, although 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," said Dr. Gouon-Evans. "By identifying where in the
viral life cycle the infection is dysfunctional, we can develop an
effective animal model of HCV." Dr. Evans and his team found that HCV was less efficient at entering
macaque cells to initiate infection compared to human cells because
changes in the macaque form of a certain cell surface receptor rendered
it less functional than the human version. This cell entry block could
be overcome by expressing the human version of this receptor in macaque
cells. Furthermore, HCV infection of normal macaque cells was greatly
enhanced by changes to the virus that loosened its requirements for that
receptor. "Our discovery shows that by manipulating either host or viral genetics
we can efficiently infect macaque cells," said Dr. Evans. "These
findings may open doors for the field of HCV research, lead to new
animal models, and hopefully vaccines and therapies." Next, Dr. Evans plans to take these experiments out of petri dishes by
attempting to infect macaques in vivo with the mutant HCV that can use
the receptors this animal naturally expresses. If successful, this work
would provide a new, much-needed animal model for HCV studies and
vaccine development.
Source:Eurekalert
Source:Eurekalert
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