Stress-induced changes in pathophysiology and interferon gene expression during primary HSV-1 infection.

Herpes simplex viruses (HSV) are the cause of the most common clinically recognized herpesvirus infections. The severity and duration of the primary HSV infection have been correlated with the frequency and severity of subsequent recurrences. Reactivation of latent HSV-1 can occur as a result of physical or emotional stress; however, the effects of stress on the modulation of the clinical pathophysiology of primary HSV-1 infections are not well understood. Although it is known that stress can be immunosuppresive, the immunological mechanisms by which stress modulates early immune responses, such as type I interferon gene expression during a primary HSV-1 infection are still not understood. It was hypothesized that due to suppressed early immune responses, stress would increase the severity of a cutaneous primary HSV-1 infection. In this investigation, a cutaneous HSV-1 model in the SKH-1 mouse was characterized and utilized to study the effect of restraint stress on the modulation of the clinical pathophysiology of primary HSV-1. Despite prolonged viral replication at the site of primary infection, restraint stress decreased the clinical severity of primary HSV-1 in the skin of SKH-1 mice. A decrease in type I and type II IFN expression was found in the skin of acutely infected restrained mice when compared to controls at day 3 post-infection using competitive RT-PCR. Using the glucocorticoid-receptor antagonist RU486, IFN-beta and INF-gamma expression were restored in restrained animals to control levels. Treatment with RU486 also increased the clinical severity of the cutaneous infection to control levels in restrained mice. Thus, RST masked the severity of an HSV-1 infection by decreasing its clinical signs while impairing the ability of the host to control viral replication prolonging the infectious period.