Alberta University. Canada: UAlberta gastroenterologist explores viral connection to primary biliary cirrhosis.
For the past decade, Andrew Mason has held fast to an idea that much of the
world’s scientific community had long since dismissed. Mason, a
professor of medicine at the University of Alberta’s Faculty of Medicine & Dentistry
and a gastroenterologist at the U of A Hospital, was convinced that a
betaretrovirus triggered an autoimmune liver disease. The agent was
previously linked with cancer, but the low levels of virus made it too
difficult to convincingly demonstrate infection. Most researchers don't
believe that betaretroviruses can infect humans—but now Mason is glad he
stuck with it.
In a new study published in the February edition of the journal Alimentary Pharmacology and Therapeutics,
Mason, along with colleague Gane Wong, a professor of bioscience and
medicine at the U of A, found that human betaretrovirus (HBRV) infection
is commonly observed in the cells of patients with primary biliary
cirrhosis (PBC), a liver disease categorized as autoimmune in nature.
According to Mason, the finding provides a level of proof that the virus
infects humans and also demonstrates a connection between the virus and
liver disease.
“Our publication shows that this virus inserts its DNA into the human
genome, where we found the junction regions of virus integration in
cells of the biliary epithelium, the site of disease,” explains Mason.
“This is the gold standard for demonstrating retrovirus infection. We
actually saw over 1,500 unique virus integrations in patients’ samples.
So that settles an ongoing debate since the 1970s saying that a
betaretrovirus like ours is not a human pathogen.”
The idea that HBRV could cause a form of cancer was first brought up
in the 1970s. However, because the virus was found at such low levels at
the time, the scientific community could not agree on whether it was a
true infection. Mason says the discussion reached a stalemate in the
1980s and was eventually ignored once the HIV epidemic emerged. In 1998
the U of A researcher began examining HBRV and its connection to PBC,
eventually publishing findings linking the two in the journal Proceedings of the National Academy of Science.
Those findings were called into question after another group was unable
to find the virus within the liver of PBC patients and challenged the
study. Now, more than a decade later, Mason says his team is able to
offer further and more detailed proof through the advancement of
technology and the use of gene sequencing.
“We always thought that autoimmune diseases like PBC looked like
virus infections underneath the microscope, but people have been unable
to find viruses. Because they found autoantibodies they assumed these
were autoimmune diseases. But patients with hepatitis C virus make
autoantibodies, and no one calls this an autoimmune disease. So we are
taking the same approach with PBC as with hepatitis C virus
infection—try and knock out the virus with antiviral therapy.”
Primary biliary cirrhosis is a rare disease that affects the bile
duct in the liver. It occurs in up to one in 500 middle-aged women and
is found in about 10 per cent of all patients needing liver transplants.
Despite the progress being made, Mason says HBRV has still not yet been
fully linked as the cause of disease. His team is in the midst of a
randomized controlled trial that he hopes will provide further proof.
The researchers are following PBC patients who are taking antiretroviral
therapy to see whether they show clinical improvement.
“Loss of virus equals loss of disease. We have to show that.”
Mason believes the findings offer new avenues of research for future
clinical treatment. And though answers won’t come quickly, he says they
are emerging, offering hope to patients suffering from PBC.
“We’ve seen some improvement in patients with recurrent PBC following
liver transplantation using antiviral therapy. Our CIHR funding now is
for testing newer medicines in the lab to find better treatments.”
Research funding was provided by the Canadian Institutes of Health
Research, Alberta Heritage Foundation for Medical Research, Alberta
Cancer Foundation, Canadian Liver Foundation, Alberta Health Services
and the Li Ka Shing Institute of Virology.
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