An international team of scientists led by Harvard Medical School’s Joslin Diabetes Center has identified four viruses that can produce insulin-like hormones. Reported in the Proceedings of the National Academy of Sciences, the discovery brings new possibilities for revealing biological mechanisms that may cause disease.

By analyzing large research databases that hold viral genomic sequences, Joslin Diabetes Center’s chief academic officer Professor Ronald Kahn and co-authors found that various viruses can produce peptides that are similar in whole or in part to 16 human hormones and regulatory proteins.

“What really caught our attention were four viruses (members of the family Iridoviridae) that had insulin-like sequences,” Professor Kahn said.

“These viruses are definitely known to infect fish and amphibians, but they are not known to infect humans,” he added.

“However, it’s possible that humans get exposed to these viruses through just eating fish. Nobody has checked directly whether under some conditions the viruses could either infect cells or be at least partly absorbed through the gut intestine.”

To find out if they could be active in mammals, the scientists chemically synthesized the viral insulin-like peptides (VILPs).

Experimenting in mouse and human cells, they studied whether the VILPs could act like hormones.

Their experiments proved that the VILPs could indeed bind to human insulin receptors and receptors for a closely related hormone called insulin-like growth factor 1 (IGF-1).

These are the critical proteins on the cells that tell them to take up glucose and to grow.

Additionally, the peptides could stimulate all of the signaling pathways inside the cells that were stimulated by human insulin and IGF-1.

And mice injected with the viral peptides exhibited lower levels of blood glucose, another sign of insulin action.

Moreover, analysis of databases of viruses found in the human intestine showed evidence that humans are exposed to these viruses.

“This finding is the tip of an iceberg. There are thought to be more than 300,000 viruses that can infect or be carried in mammals, and only 7,500 or so of these, or about 2.5%, have been sequenced,” Professor Kahn said.

“Thus, we certainly expect to find many more viral hormones, including more viral insulins, in the future.”

“This research also opens up a new aspect to study in type 1 diabetes and autoimmunity,” he added.

“It may be that these or similar microbial insulin-like molecules could be an environmental trigger to start the autoimmune reaction in type 1 diabetes.”

“On the other hand, you could also imagine that this might desensitize the immune response and could be protective.”

“Our research may help open up a new field that we might call microbial endocrinology,” said Dr. Emrah Altindis, also from Joslin Diabetes Center.

“We show that these viral insulin-like peptides can act on human and rodent cells. With the very large number of microbial peptides to which we are exposed, there is a novel window for host-microbe interactions. We hope that studying these processes will help us to better understand the role of microbes in human disease.”

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Emrah Altindis et al. Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions. PNAS, published online February 21, 2018; doi: 10.1073/pnas.1721117115

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