HSV-1 infection (herpes) is associated with colonic nerve damage in mice — Might this explain reports of constipation and urinary retention in humans similarly infected with that — or other members of the herpes virus family?

© 2016 Peter Free

Citation — to study

William Khoury-Hanold, Brian Yordy, Philip Kong, Yong Kong, William Ge, Klara Szigeti-Buck, Alexandra Ralevski, Tamas L. Horvath, and Akiko Iwasaki, Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality, Cell Host & Microbe 19(6): 788–799, DOI:  10.1016/j.chom.2016.05.008 (08 June 2016)

Citation — to press release

Ziba Kashef, Constipated? Study finds surprising cause, Yale News – Yale University (08 June 2016)

In a mouse HSV-1 model

From the abstract:

Herpes simplex virus 1 (HSV-1), a leading cause of genital herpes, infects oral or genital mucosal epithelial cells before infecting the peripheral sensory nervous system. The spread of HSV-1 beyond the sensory nervous system and the resulting broader spectrum of disease are not well understood.

Using a mouse model of genital herpes, we found that HSV-1-infection-associated lethality correlated with severe fecal and urinary retention. No inflammation or infection of the brain was evident.

Instead, HSV-1 spread via the dorsal root ganglia to the autonomic ganglia of the enteric [meaning gut] nervous system . . . in the colon.

[Enteric nervous system] infection led to robust viral gene transcription, pathological inflammatory responses, and neutrophil-mediated destruction of enteric neurons, ultimately resulting in permanent loss of peristalsis and the development of toxic megacolon [see here].

Laxative treatment rescued mice from lethality following genital HSV-1 infection. These results reveal an unexpected pathogenesis of HSV associated with ENS infection.

© 2016 William Khoury-Hanold, Brian Yordy, Philip Kong, Yong Kong, William Ge, Klara Szigeti-Buck, Alexandra Ralevski, Tamas L. Horvath, and Akiko Iwasaki, Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality, Cell Host & Microbe 19(6): 788–799, DOI:  10.1016/j.chom.2016.05.008 (08 June 2016) (at Abstract) (paragraph split)

Implications for human medicine

From Yale University:

Individuals with herpes have reported seemingly unrelated symptoms such as constipation and urinary retention (inability to empty the bladder), but the mechanism was not understood.

The research team, led by Akiko Iwasaki . . . decided to investigate using mice models of herpes simplex virus-1, the dominant cause of genital herpes in the United States.

They found that the herpes virus spread from the genitals to nerves in the spinal cord, and then on to neurons in the colon, killing them. The damage to the colonic neurons prevented the movement of food along the digestive tract, leading to an enlarged colon and disease.

While the effects in mice are distinct from what happens in people with herpes, the study reveals a previously unrecognized disease process.

“The key finding is that there is this unexpected infection in the neurons in the colon wall after herpes infection,” said Iwasaki.

“Other members of the herpes virus family, including Epstein-Barr virus, chicken pox virus, and cytomegalovirus have been found in the neurons of the colon of people with unexplained chronic constipation.

When doctors can’t figure out the cause of these chronic intestinal conditions, one thing to look at is a viral infection.”

Ziba Kashef, Constipated? Study finds surprising cause, Yale News – Yale University (08 June 2016) (typo-corrected extracts)

The moral? — Sneaky, those viruses

Perhaps someday we will be able to more finely tune or immune systems.