Effects of HSV-1, a neurotropic virus, on the hypothalamic-pituitary-adrenocortical axis in rats.

It is well established that the hypothalamic-pituitary-adrenocortical (HPA) axis is activated during systemic viral diseases. In this study we examined the effects of a neurotropic virus, herpes simplex virus type 1 (HSV-1), on the HPA axis in male rats. Following corneal inoculation with HSV-1, the virus invaded the nervous system and replicated in the brainstem without clinical signs of disease. During this asymptomatic brainstem infection with HSV-1, significant changes were found in the function of the HPA axis: On days 3, 7 and 14 post-infection (p.i.) basal ACTH and corticosterone (CS) levels were markedly elevated, and photic stressful stimulation failed to further increase the levels of these hormones. In addition, the elevated basal serum levels of ACTH and CS could not be suppressed by pretreatment with dexamethasone. The content of CRF-41 in the paraventricular nucleus of the hypothalamus and in the median eminence measured at 6 days p.i. was similar to that of vehicle inoculated rats. By 4 weeks p.i. the basal levels of ACTH and CS returned to normal and these animals responded to photic stimulation and dexamethasone similar to vehicle inoculated rats. Systemic (intraperitoneal) inoculation of HSV-1 did not induce any changes in the HPA axis responses. We therefore suggest that asymptomatic acute infection of the brainstem with HSV-1 may affect brain regions involved in the regulation of the HPA axis, and that those effects are mediated centrally and not by a systemic mechanism.