Acute and persistent rabies virus infection of mouse neuroblastoma-rat glioma hybrid cells (ii) the signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective.Cells of the mouse neuroblastoma-rat glioma hybrid line NG-108-15 (108CC-15) have a variety of membrane receptors on their surfaces, including opiate receptors. Many fundamental studies of opiate receptor functions have been carried out with these cells and have enriched our knowledge of the biochemical basis of opiate receptor function (1-7). These cells are very suitable for studying the effect of persistent infections by neurotropic viruses on receptor specific functions in cells derived from the central nervous system. Unlike acute infections, these persistent infections cause no destruction of the cells and cause only transient changes, if any, in the growth parameters of these cells. In the case of rabies virus pathogenesis of animals and man it is supposed that the observed central nervous deficiencies are mainly caused by the interaction of the virus with its neuronal host cells, because pathological examination shows little immune-mediated cell destruction in the infected region of the brain (8). It appears that the limbic system plays an important role during rabies virus pathogenesis, thus giving rise to the term "limbic tropism" (8). It is known that the limbic system contains large numbers of encephalinergic neurons with a high concentration of opiate receptors (9, 10). To investigate the possible influence of rabies virus infection on opiate receptor mechanisms we established acute and persistent rabies virus infections in NG-108-15 cells. We have previously observed that the normal inhibitory effect of the agonist binding to opiate receptor on adenylate cyclase activity was lost when the infected cells were incubated simultaneously with prostaglandin E1 as an adenylate cyclase stimulatory hormone and with opiates as agonists for the cAMP formation-inhibiting function of opiate receptors (11). Further studies have demonstrated a loss of 30-40% of affinity of the opiate receptors in NG-108-15 cells in acute infections. This was increased to 80-90% in long-time persistence. The number of the opiate receptors was unchanged, however, in both cases (12).According to Cassel and Selinger (13), adenylate cyclase is activated by binding of GTP to the stimulating regulatory protein Ns. This complex formation is increased after the occupation of stimulating hormone receptors by their appropriate hormones. But after occupation of inhibiting receptors, like opiate receptors, by their agonists the GTPase activity of an inhibiting regulatory GTP-binding protein N1 of the adenylate cyclase system is stimulated (7). A model of adenylate cyclase regulation by inhibiting and stimulating regulatory coupling components (N, and Ns) has been recently discussed by Jakobs and Schultz (14). Hamprecht and coworkers found in the opiate receptor system of NG-108-15 (10...