Researchers found that a seemingly innocuous virus
can provoke immune responses to a dietary protein in
Patients with celiac disease showed high levels of
antibodies to the virus.
The results suggest that viruses may play a role in
initiating immune responses against gluten.
Celiac disease is a digestive disorder that’s
triggered by eating foods containing gluten—a
protein common in foods such as bread, pasta,
cookies, and cakes.
When a person with celiac disease eats or drinks
anything with gluten, the body’s immune system
attacks the inside of the small intestine.
The damage from this attack keeps the body from
absorbing needed nutrients.
If left untreated, celiac disease can lead to
malnutrition, anemia, weakened bones, and other
Researchers don’t know exactly what triggers celiac
disease. Certain genes and other factors, such as
things in the environment, can lead to celiac
Viral infections have been suggested as a possible
A team led by Dr. Bana Jabri at the University of
Chicago and Dr. Terence S. Dermody at the University
of Pittsburgh School of Medicine investigated
whether a common but harmless type of virus that
people are frequently exposed to, called reoviruses,
can prompt sensitivity to dietary proteins.
The team studied two different strains of reoviruses
(T1L, which can infect the intestine, and T3D-RV,
which was engineered to infect the intestine) in
Both strains triggered an immune response that
protected the mice against the infection.
However, animals infected with TL1 also showed
altered immune responses in the gut.
Both type 1 interferon (IFN) signaling and
interferon regulatory factor 1 (IRF1) expression
IRF1 regulates gene transcription and plays a key
role in oral tolerance, or the suppression of immune
responses to an orally delivered substance, like
After being infected with T1L, susceptible mice lost
their oral tolerance to a dietary protein.
A follow-up gene expression analysis showed this was
triggered by specific changes in immune signaling
These changes both block the mechanism that
maintains tolerance to dietary proteins and promote
the immune reaction against them.
The team next investigated whether patients with
celiac disease had been exposed to reoviruses.
Patients with celiac disease had higher levels of
reovirus antibodies than controls.
Patients on a gluten-free diet also had higher
levels of reovirus antibodies and IRF1 levels in
their small intestines, suggesting reovirus
infection may lead to long-lasting gene expression
“This study clearly shows that a virus that is not
clinically symptomatic can still do bad things to
the immune system and set the stage for an
autoimmune disorder, and for celiac disease in
particular,” Jabri says.
“However, the specific virus and its genes, the
interaction between the microbe and the host, and
the health status of the host are all going to
matter as well.”
More work will be needed to better understand how
reovirus and possibly other viruses might provoke
food intolerance. The results may lead to new
prevention and treatment strategies.
The study was supported by NIH’s National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK)
and National Institute of Allergy and Infectious
Diseases (NIAID), among others. Results were
published in Science on April 7, 2017.
For more information
Reovirus infection triggers inflammatory responses
to dietary antigens and development of celiac
disease. Bouziat R, Hinterleitner R, Brown JJ,
Stencel-Baerenwald JE, et al., Science. 2017 Apr
7;356(6333):44-50. doi: 10.1126/science.aah5298.