Social Stress Causes Dormant Herpes Virus To Resurface In Mice

July 31, 1998

COLUMBUS, Ohio -- New research in mice shows that changes in social interactions can stimulate a dormant herpes virus to resurface.

In a series of experiments, 40 percent of mice with latent herpes had their virus reactivated when their social structure was reorganized, leading to conflicts among the mice.

The herpes virus was most prevalent in the dominant mice, who were involved in the most aggressive social interactions.

While the study may have some implications for human health, it also provides researchers with a good animal model to study the relationship between stress and immunity.

"No animal model existed to study and really understand the mechanisms of how the virus works," said Ronald Glaser, professor of medical microbiology and immunology at Ohio State University. "Now that we have the model, we can start analyzing and studying the mechanisms of different kinds of stress and how it can affect virus latency."

This research supports the idea that stressful life events, such as changes in leadership at the workplace, can significantly suppress the immune system and increase the incidence of infectious diseases.

"When a new boss comes in, people worry if their position will be the same, if the order of dominance will change," Glaser said. "We think that's what is going on when we socially reorganize these mice."

The research, published in a recent issue of the Proceedings of the National Academy of Sciences, showed that stress caused by social reorganization triggered a dormant herpes simplex virus type 1 (HSV-1) infection. HSV-1 causes cold sores around the mouth and on the face in humans and genital disease.

Glaser conducted the study with David Padgett, assistant professor of oral biology, and John Sheridan, professor of oral biology and preventive medicine. Both are with Ohio State.

The model, which used male mice, allowed the researchers to study how a body physically interprets certain stressors.

The researchers infected mice with HSV-1 and subjected the animals to two stressful situations. One situation involved restraining the animals for portions of eight days. The other reorganized the social hierarchy of the mice by placing a dominant mouse in a new cage.

Glaser said he was surprised with the findings. "Only one of the two stressors, social reorganization, resulted in a significant reactivation of the herpes virus," he said. While 40 percent of mice showed herpes reactivation when faced with social stress, only 8 percent of the mice who were restrained were similarly reactivated.

Although unsure why the social reorganization caused full-blown herpes, the researchers speculate that exposure to different kinds of stress causes different physiological changes in the body.

"The assault of daily stresses throws our bodies into somewhat of a disarray, so our bodies respond with physiologic adaptations in attempts to restore their normal state," Padgett said.

Glaser and his colleagues looked at the levels of one stress hormone in particular -- corticosterone. Corticosterone levels almost doubled in the socially reorganized mice as compared to controls.

The social stress most affected dominant mice, who faced the most conflict in their new social situation. Results showed 85 percent of the dominant mice had herpes reactivation, compared to 30 percent of the subordinate mice.

"The dominant mice were much more likely to have a higher rate of virus reactivation," Sheridan said. The herpes virus hibernates inside the body's cells and remains dormant there until it gets a signal from the body. In this case, social stress caused the virus to reactivate.

"Our long-term goal is to develop a therapeutic strategy to prevent herpes virus activation," Padgett said.

Other members of the research team were Julianne Dorne and Jessica Candelora, both of Ohio State's medical microbiology and immunology department, and Gary Berntson, professor of psychology at Ohio State.

The research was supported by grants from the Ohio State Comprehensive Cancer Center, the National Institute of Mental Health and the MacArthur Foundation Mind-Body Network.
Contact: Ronald Glaser, (614) 292-5526;
David Padgett, (614) 292-2012;
John Sheridan, (614) 292-2012;

Written by Holly Wagner, (614)292-8310;

Ohio State University

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