Research into range of mutations provides clues to improve treatment
Research into range of mutations provides clues to improve
treatment
A team of international researchers, led by Matthias Götte from
McGill’s Department of Microbiology and Immunology, believes it has
found a key factor in understanding why certain drug-resistant
strains of the hepatitis C virus are seen so frequently, while
others are rarely detected.
It has been estimated that 170 million people around the world
are infected with the hepatitis C virus (HCV). Close to 300,000 of
them live in Canada. Chronic infection with the virus is associated
with severe liver disease, including cirrhosis and cancer. Unlike
hepatitis A and B, there is currently no vaccine to prevent people
from catching the disease. Although new medications show great
promise in curing HCV infection, the virus is able to develop
resistance to each class of antiviral drugs. And as a result,
treatment may fail.
It was already known that humans are not infected by a single
species of virus, but rather by billions of different, mutant
viruses that sometimes differ from one another only by a single
nucleotide, i.e. the basic building blocks of viral RNA. The
researchers have now demonstrated that the viral polymerase, the
enzyme responsible for copying sequences from RNA, is inaccurate in
the way it replicates these sequences and as a result generates
mutations when connecting one nucleotide after the other. “The
surprising finding we had is that some mutations are much more
easily made than others,” says Götte.
They next submitted HCV RNA samples taken from infected patients
to sequence analyses and were able to distinguish between rare and
common types of mutations. Together, the data suggest that the bar
for the development of drug resistance is much higher if rare
mutations are involved. This study has therefore important
implications for the development of potent drug combinations that
are less likely to result in the emergence of resistance.
The research was funded by: Cancer Research Society, Canadian
Institutes of Health Research
Career awards and stipends were provided by: Fonds de Recherche
en santé du Québec, Canadian Institutes of Health Research, and the
National Canadian Research Training Program in Hepatitis C.
The paper describing the research was published by the
Proceedings of the National Academy of Sciences (PNAS).
To read an abstract of the paper: http://www.pnas.org
More news from McGill University: http://www.mcgill.ca/newsroom/
PHOTO: High magnification micrograph of a liver with
cirrhosis, a complication of hepatitis C. (Wikimedia
Commons)