virusInfection with a common virus (without symptoms) could be one of the first steps towards developing coeliac disease, an autoimmune condition that damages the gut.

Coeliac disease involves the immune system treating gluten as an antigen ( foreign substance which induces an immune response)  and attacking it and has generally been thought to be a genetic disease. However, there is some evidence that the onset of the condition may be linked to people experiencing viral infections. These may include infection by adenoviruses, which cause colds, rotaviruses, which can cause diarrhoea, and the hepatitis C virus.

Now there is experimental evidence that some viruses may indeed prompt the onset of coeliac disease. Bana Jabri at the University of Chicago, Illinois, found that exposing mice to a common reovirus called T1L breaks their tolerance of gluten.

When the team fed small groups of mice gluten – they found that mice produced three times as many antibodies against the gluten over the next two days if they were also infected with reovirus.

“The reovirus changes the way the immune system sees gluten,” says Jabri. Normally, the body’s immune system learns to tolerate the wide range of substances in our food, including gluten – a protein found in wheat, rye and barley. But the team’s findings suggest that infection with a reovirus interferes with this, leading the body to mistakenly attack gluten.

“Our experiments are the first to demonstrate that a virus can induce loss of tolerance to dietary antigens,” says Jabri.

Indigestible gluten

“Instead of mounting a tolerant, non-aggressive response, the immune system in the presence of the reovirus views gluten as being dangerous, promoting a destructive inflammatory response,” says Jabri.

The researchers also found that mice infected with the T1L virus had between four times as much of an inflammatory molecule in their bodies. This molecule, called interferon regulatory factor 1, has been found at abnormally high levels in the gut linings of children with coeliac disease, and has also been implicated in instigating the condition’s onset.

Compared with other common foodstuffs, gluten is particularly likely to trigger immunological problems because it is unusually resistant to being broken down in the gut, says Jabri. Gliadin is the most difficult component of gluten to digest.

The team’s findings could explain why only a small proportion of people develop coeliac disease, which is a far more severe condition that gluten intolerances. While 40 per cent of people in the US seem to have a genetic predisposition to coeliac disease, only 3 per cent of the population – around 3 million people – have the condition. This could be because the others haven’t been exposed to a viral trigger.

“This is a fascinating study,” says David Sanders, at the University of Sheffield, UK. “Investigators have studied this ‘second-hit’ hypothesis for some time, to explain why not everyone with genetic predisposition actually develops the disease. Now the new study suggests that reoviruses might play a role.”

If studies in people confirm that reovirus can trigger coeliac disease, it could lead to new treatments, says Sanders. Jabri’s team are now working on a vaccine that might stop infections from causing coeliac disease.

Journal reference: Science, DOI: 10.1126/science.aah5298