While studying viruses best known for infecting the brain, researchers at Washington University School of Medicine in St. Louis stumbled upon clues to a conundrum involving a completely different part of the anatomy: the bowel, and why some people possibly develop digestive problems seemingly out of the blue.
The researchers found that viruses such as West Nile and Zika that target the nervous system in the brain and spinal cord also can kill neurons in the guts of mice, disrupting bowel movement and causing intestinal blockages. Other viruses that infect neurons also may cause the same symptoms, the researchers said.
The findings, published in the journal Cell, potentially could explain why some people experience recurrent, unpredictable bouts of abdominal pain and constipation—and perhaps point to a new strategy for preventing such conditions.
"There are a number of people who are otherwise healthy who suddenly develop bowel motility problems, and we don't understand why," said Thaddeus S. Stappenbeck. "But now we believe that one explanation could be that you can get a viral infection that results in your immune cells killing infected neurons in your gut. That might be why all of a sudden you can't move things along anymore."
Postdoctoral researcher and first author James White, Ph.D., was studying mice infected with West Nile virus, a mosquito-borne virus that causes inflammation in the brain, when he noticed something peculiar. The intestines of some of the infected mice were packed with waste higher up and empty farther down, as if they had a blockage.
"We actually noticed this long ago, but we ignored it because it wasn't the focus of our research at the time," said West Nile expert Michael S. Diamond. "But Jim White dug in. He wanted to figure out why this was happening."
White, Diamond, Stappenbeck and colleagues including Robert Hueckeroth, found that not only West Nile virus but its cousins Zika, Powassan and Kunjin viruses caused the intestines to expand and slowed down transit through the gut. In contrast, chikungunya virus, an unrelated virus that does not target neurons, failed to cause bowel dysfunction.
West Nile virus
Further investigation showed that West Nile virus, when injected into a mouse's foot, travels through the bloodstream and infects neurons in the intestinal wall. These neurons coordinate muscle contractions to move waste smoothly through the gut. Once infected, the neurons attract the attention of immune cells, which attack the viruses—and kill the neurons in the process.
"Any virus that has a propensity to target neurons could cause this kind of damage," said Diamond. "West Nile and related viruses are not very common in the U.S. But there are many other viruses that are more widespread, such as enteroviruses and herpesviruses, that also may be able to target specific neurons in the wall of the intestine and injure them."
The infected mice's digestive tracts gradually recovered over an eight-week time span. But when the researchers challenged the mice with an unrelated virus or an immune stimulant, the bowel problems promptly returned. This pattern echoed the one seen in people, who cycle through bouts of gastrointestinal distress and recovery. The flare-ups often are triggered by stress or illness, but they also can occur for no apparent reason.