Virus and host factors that mediate the clinical and behavioral signs of experimental herpetic encephalitis. A short auto-review.

Experimental models that mimic the clinical syndrome of human viral encephalitis and represent HSV-1 neurotropism were utilized to investigate neuro-pharmacologic changes mediating clinical and behavioral manifestations of encephalitic infection of the central nervous system with HSV-1-induced rapid activation of the hypothalamic--pituitary--adrenocortical (HPA) axis and production of brain derived interleukin-1 (IL-1) and prostaglandin E2 (PG-E2), independently of viral replication. HSV-1 infection induced clinical signs of fever, motor hyperactivity and aggressive behavior. These manifestations were dependent on a permissive action of circulating glucocorticoids and not related to the degree of viral replication in the brain. Hyperthermia and HPA axis activation were also specifically dependent on HSV-1-induced brain IL-1 and PG-E2. The chronic neurological sequel or fatal outcome of HSV-1 encephalitis may be due to viral replication and brain tissue destruction, which are dependent on virus encoded virulence genes. In contrast, the clinical and behavioral signs in the acute phase are a result of activation of neurochemical systems, including cytokines, prostaglandinds and catecholamines. Circulating glucocorticoids play an essential role in mediating the physiologic actions of HSV-1-induced brain products and the clinical syndrome of encephalitis.