Social stress and the reactivation of latent herpes simplex virus type 1

Abstract

Psychological stress is thought to contribute to reactivation of latent herpes simplex virus (HSV). Although several animal models have been developed in an effort to reproduce different pathogenic aspects of HSV keratitis or labialis, until now, no good animal model existed in which application of a psychological laboratory stressor results in reliable reactivation of the virus. Reported herein, disruption of the social hierarchy within colonies of mice increased aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and caused reactivation of latent HSV type 1 in greater than 40% of latently infected animals. However, activation of the hypothalamic-pituitary-adrenal axis using restraint stress did not activate the latent virus. Thus, the use of social stress in mice provides a good model in which to investigate the neuroendocrine mechanisms that underlie behaviorally mediated reactivation of latent herpesviruses.

Figure 1

Influence of RST stress on serum corticosterone levels. Data represent 10 a.m. serum corticosterone as measured by RIA. Baseline samples were obtained 2 days before initiation of any experimental manipulations. Mice were restrained for 16 hr on sequential evenings. Control mice were deprived of food and water for the same period of time. n = 5 animals per group at each time point.

Figure 2

Influence of social reorganization on serum corticosterone. Data represent 10 a.m. serum corticosterone as measured by RIA. Baseline samples were obtained 2 days before initiation of any experimental manipulations. For social reorganization, dominant animals were identified and placed in new cages at 6 p.m. the evening before blood sampling. n = 5 animals per group at each time point.