Subacute sclerosing panencephalitis (SSPE) is a fatal disease of children caused by a persistent infection of the central nervous system (CNS) by a defective form of measles virus. It is virtually unique in the realm of slow virus diseases of man in that the etiologic agent has been isolated and identified and a great deal is known about the immunological, epidemiological, and molecular aspects of its pathogenesis. Further, several workable animal models have been developed for SSPE. Thus, SSPE can justifiably be considered a """"""""model"""""""" slow virus disease, and the insights and new concepts that emerge from its study can be expected to greatly facilitate the investigation of other proven or suspected slow virus diseases of man. The proposed studies canter around a hypothetical model for the pathogenesis of SSPE. The model is based upon three basic postulates: 1. All strains of measles virus are capable of spontaneously generation variants that directly induce defective, cell- associated states of infection in permissive cells. 2. These defective viral variants create infection states within the CNS that are resistant to clearance by specific immunological mechanisms but and relatively susceptible to suppression by interferon (IFN). 3. Clinical disease, e.g. SSPE, results when a viral form with increased resistance to suppression by IFN arises during persistent CNS infection. This hypothetical model for the pathogenesis of SSPE integrates a heretofore largely unstudied infection component, i.e. interferon; accounts for many observations concerning measles virus and CNS disease, e.g. the presence of measle genome in the CNS of healthy individuals; and makes numerous testable predictions, e.g. that wild-type strains of measles virus should be more susceptible to suppression by IFN than are SSPE derived strains. The testing of this hypothetion model using both in vitro and in vivo experimental systems provides the basis and this research proposal.
| Carrigan, D R; Knox, K K (1990) Identification of interferon-resistant subpopulations in several strains of measles virus: positive selection by growth of the virus in brain tissue. J Virol 64:1606-15 |
