Stress, Corticotropin and Neuroimmune Interactions

Acute Effects of Purified and UV-Inactivated Herpes simplex Virus Type 1 on the Hypothalamo-Pituitary-Adrenocortical Axis
Tamir Ben-Hur^a, Ron Cialic^a, Anna Itzik^a, Raz Yirmiya^b, Joseph Weidenfeld<sup>a

a</sup>Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University, and
^bDepartment of Psychology, Hebrew University, Jerusalem, Israel

Address of Corresponding Author

Neuroendocrinology 2001;74:160-166 (DOI: 10.1159/000054682)

  Key Words

• Corticotropin
• Adrenal steroids
• Interleukins
• Herpes virus
• Paraventricular nucleus
• Hypothalamo-pituitary-adrenal axis

  Abstract

Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. We have previously demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA) axis activation. In this study we characterized the acute effects of HSV-1 on the HPA axis occurring before viral replication and appearance of clinical signs of encephalitis. Since in previous studies we used crude virus preparations which may contain immune factors produced by the infected cells, we tested here the effects of purified HSV-1 virions. HSV-1 was propagated on Vero cells and virions were purified by centrifugation in sucrose gradients. Inactivation of viral infectivity was achieved by UV-irradiation, which caused a million-fold decrease in virus titer, as determined by plaque assay. Intracerebroventricular (ICV) inoculation of crude or purified virions induced a dose dependent increase in serum corticosterone and corticotropin (ACTH). This effect was maximal within 3.5 h postinfection and lasted for 72 h. ICV inoculation of UV-inactivated purified virions caused a marked increase in serum corticosterone and ACTH at 3.5 h, but in contrast to the effect of the active virus, the hormone levels gradually decreased at 24 h, and returned to basal levels at 72 h postinfection. HSV-1-induced HPA axis activation at 3.5 h was completely abolished by pretreatment with interleukin-1 receptor antagonist, injected ICV. Adrenalectomized rats failed to respond to ICV inoculation of purified HSV-1 by increase in ACTH. In contrast, these rats responded to ICV injection of LPS. In conclusion: (1) HSV-1 can acutely activate the HPA axis before and independently of any viral replication; (2) HSV-1-induced HPA axis activation depends on a permissive action of circulating glucocorticoids and on host derived brain interleukin-1.

Copyright © 2001 S. Karger AG, Basel

  Author Contacts

Tamir Ben-Hur
Department of Neurology
Hadassah-Hebrew University Hospital, Ein-Kerem
PO Box 12000, Jerusalem 91120 (Israel)
Tel. +972 2 677 6941, Fax +972 2 643 7782, E-Mail tamir@hadassah.org.il

  Article Information

Received: Received: December 28, 2000
Accepted after revision: April 26, 2001
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 1, Number of References : 20