1P-S4-1文本框: NEW CONCEPTS IN THE NEUROPATHOGENESIS OF VIRAL INFECTIONS Peterson PK, Hu S, Gekker G, Sheng WS, Cheeran M, Lokensgard J Neuroimmunology Research Laboratory, Minne0apolis Medical Research Foundation and University of Minnesota Medical School, Minneapolis, Minnesota USA Despite the importance of viral infections of the brain in children, antiviral therapy is lacking for most causes of viral encephalitis. To better understand the neuropathogenesis of viral infections, a number of research groups have been studying the cellular and molecular mechanisms involved in defense and damage of the brain. The classic concept of the brain as an “immunologically privileged site" has been modified by these studies. Within the brain parenchyma, glial cells (astrocytes and microglia) greatly outnumber neurons, and these glial cells appear to function as an endogenous immune system. Research in our laboratory has focused on interactions of HIV, herpes simplex virus (HSV), and cytomegalovirus (CMV) with highly purified cultures of human microglia, astrocytes, and neurons. Striking differences have been found with these viruses in terms of their abilities to replicate in these brain cell types, as well as in production of cytokines and chemokines by glial cells in response to these viruses. Also, certain cytokines and chemokines profoundly inhibit viral replication in microglia, astrocytes, and neurons. In addition to the antiviral properties of cytokines and chemokines, we have found that psychotropic drugs (opioids, benzodiazepines, thalidomide, and certain natural products) can suppress the replication of HIV in microglial cell cultures. Also, other investigators have shown that morphine protects animals against neuropathogenic HSV. The results of our studies suggest that in addition to developing antiviral agents that target viruses directly, the pharmaceutical industry should consider exploiting agents such as cytokines, chemokines, and psychopharmacologic drugs that may act by making brain cells less habitable for viruses or by inhibiting inflammatory cell-mediated brain damage.