Viral trigger may underlie development of celiac disease

By Sally Robertson, B.Sc.Apr 10 2017

Reovirus, which commonly infects humans without causing any symptoms, may trigger an immune response to gluten that causes celiac disease, report US researchers.

In a study published in Science, orally infecting mice with the seemingly benign virus triggered an immune response to gluten and led to celiac disease symptoms in the rodents.

The study raises the possibility that, in the future, vaccines could be used to prevent celiac disease and other autoimmune disorders such as type 1 diabetes.

Virologist Herbert Virgin (University of Washington), who collaborated with some of the study authors but was not involved in the research says: “It’s been hypothesized for decades that virus infection can trigger autoimmune processes. This study provides an example of that phenomenon and some mechanistic insight into how this might work for celiac disease.”

For the study, lead author Bana Jabri (University of Chicago Celiac Disease Center) and colleagues orally infected mice with two different human reovirus isolates and showed that genetic differences between the virus strains led to different interactions with the immune system.

The type 1 Lang (TIL) strain, which naturally infects the guts of humans and mice, triggered an increased production of antibodies against the virus, as well as an inflammatory response to gluten when the mice were fed a diet containing the protein. However, mice infected with a version of type 3 Dearing (T3D), a genetically modified reovirus strain, did not develop an inflammatory response or a loss of gluten tolerance.

Microbiologist Julie Pfeiffer (University of Texas Southwestern Medical Center), who was not involved in the study, says: “Using two reovirus strains with different inflammatory phenotypes was absolutely key, allowing the authors to untangle a wide array of potential confounding variables.”

“We now have a clue that reovirus might be one trigger for celiac disease,” states co-author Terence Dermody (Pediatrics Department at the University of Pittsburgh School of Medicine, Pennsylvania).

“The potential mechanism is that when gluten is introduced right at the time that an asymptomatic reovirus infection is taking hold, that causes the immune system to treat the gluten as foreign, eliciting an immune response against it.”

Dermody adds that the team is now in a position to precisely define the viral factors responsible for the induction of the autoimmune response.

Alessio Fasano (Massachusetts General Hospital for Children, Boston), who was also not involved in the study, says: “If confirmed by clinical studies, this link between celiac disease and reovirus is exciting because it identifies a possible target for vaccine prevention.”