The principal objective of these studies is to determine host and viral factors which influence genetically-controlled murine resistance to, and recovery from street rabies virus (SRV) infections following viral invasion of the central nervous system (CNS). In vitro studies have shown that neither immune serum nor monoclonal antibodies had any effect on intracellular replication or spread of virus from parent to progeny cells during the course of cell division. In contrast, the cell-to-cell spread of SRV, challenge virus standard and ERA rabies viruses from infected to adjacent uninfected cells was inhibited by greater than 99% in both neuronal and non-neuronal cells by antirabies virus immune serum and neutralizing anti-glycoprotein monoclonal antibodies. Non-neutralizing anti-nucleocapsid monoclonal antibodies did not inhibit cell-to-cell viral spread. A better understanding of the factors involved in inhibiting virus spread is essential to our deciphering how resistant strains of mice immunologically or nonspecifically (i.e., interferon) control rabies virus infections following viral invasion of the CNS. Likewise, an investigation of the importance of cellular immunity in the resistance of SJL/J mice to SRV has been initiated with the development of a potential H-2s target cell that is readily infected with rabies virus. Apathogenic SRV variants have been produced by culturing virus with neutralizing anti-glycoprotein monoclonal antibodies. Virulent and avirulent viruses are being used in comparative pathogenesis studies in A/WySn mice to determine the reasons for their 100% susceptibility to SRV. Continuing pathogenesis studies have shown that high titers of interferon were present in spinal cords of resistant SJL/J mice at approximately the same time the spread of SRV from the spinal cord to the brain ceased. No interferon was detected in cerebrospinal fluids, brains or sera, suggesting that the spinal cord interferon was locally produced. The importance of this interferon as it relates to the failure of SRV to ascend within the CNS of rabies resistant mice is being actively pursued.
