Stress and Herpes Reactivation in Mice and Men
Stress and Herpes Reactivation in Mice and Men
ABSTRACT & COMMENTARY
Synopsis: Behavioral stress resulted in an increased frequency of HSV-1 reactivation in male mice, consistent with the belief that stress can reactivate herpes simplex infection in humans.
Source: Padgett DA, et al. Social stress and the reactivation of latent herpes simplex virus type 1. Proc Natl Acad Sci USA 1998;95:7231-7235.
It is commonly believed that emotional stress can cause reactivation of herpes simplex infection. Padgett and colleagues have worked to elucidate the effects of various stressors in the murine model of latent herpes simplex virus type 1 (HSV-1) infection. Earlier work showed that restraint-stressed mice (which had been placed in 50 mL centrifuge tubes for 16 hours per day) had decreased natural killer cell lysis and decreased generation of HSV-specific cytotoxic T lymphocytes, which were associated with an increase in viral replication (HSV keratitis or labialis).
This study examined the role of psychosocial stressors on the reactivation rate of latent HSV-1 infection in BALB/c male mice. After viral latency was established (4-5 weeks post-infection), social disruption of mice colonies was caused by moving dominant animals from cage to cage, resulting in disruption of established heirarchies and levels of aggression. This was associated with elevations in basal cortisol levels, such that by the fourth cycle of reorganization, cortisol levels had increased four-fold (high enough to result in immunological down-regulation).
HSV-1 reactivation occurred in 41.7% of socially stressed animals, as demonstrated by ocular viral shedding and positive eye swabs, compared with 43.7% of UV irradiated animals, and 56.7% of mice who were both irradiated and stressed. In contrast, 8% of the restraint-stressed mice and none of the mice in the control cages, who were deprived of food and water but were allowed to move freely about their cage, had evidence of viral shedding.
COMMENT BY CAROL A. KEMPER, MD
Previous studies of HSV have been hampered by the lack of a convenient animal model of disease. Earlier murine studies indicated that reactivation HSV keratitis could be induced in up to 80% of animals by UV radiation and corticosteroid eye drops, but the exact pathogenetic mechanisms underlying the reactivation was not clear. Just by reorganizing mouse colonies in this study, Padgett et al have created an excellent animal model in which a behavioral stressor led to an increased frequency of HSV reactivation, confirming that old wive's tale that stress alone can trigger an HSV outbreak-at least in males, since this study was limited to male mice.
Interestingly, in all three experiments, the dominant mouse in each stressed-out cage was more than twice as likely (85.7%) to show signs of viral reactivation as the subordinate mice (30%). Dominant mice, the alpha males, were more likely to be involved in dangerous confrontations and had the greatest risk of injury, at least as long as they attempted to defend their dominant social status. Another reason for all those alpha males out there to take a breather-or at least stick to their established territory.
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