Virus-Host Cell Relationships in Measles-Infected Cultures of Central Nervous Tissue

Abstract
Cultures of hamster cerebellum were infected with the Edmonston strain of measles virus for up to 72 days and studied both virologically and ultrastructurally. The yield of infectious virus was maximal between 10 and 30 days PI. Significant amounts could still be detected after 68 days PI. Ultrastructurally, it could be seen that neurons degenerated early in the course of infection. Demyclination and oligodendroglial cell death followed. A mat of fibrous astrocytes persisted at 72 days PI which still synthesized infectious virus. With the exception of active replication, viral appearances essentially mimicked those described in related, naturally occurring conditions, namely, measles encephalitis, SSPE, and canine distemper. In addition, the pathologic changes evoked by measles infection in vitro shared much in common with those seen in measles affected CNS tissue in situ. The pathogenesis of measles virus infection of the central nervous system (CNS) has gained considerable attention in recent years (9). The recent recovery of measles virus from brain tissue of patients with subacute sclerosing panencephalitis (SSPE) (7, 11, 17, 19) confirmed the previous immunological evidence indicating its presence (8). These data gave impetus to the study of other diseases, in which the involvement of measles virus has been suspected on the basis of immunological studies, e.g., multiple selerosis (2). These suspicions have led to a series of studies on virus-host cell relationships in measles-infected CNS tissue. Measles virus morphogenesis in infected cultures of hamster cerebellum and dorsal root ganglion has been previously investigated (22, 23). Measles-infected hamster cerebellum was studied for periods up to 39 days post-inoculation (PI) and electron microscopic examination of these cultures documented the development of intranuclear and intracytoplasmic viral nucleocapsid material. Budding viral particles were also observed after 5 days PI and persisted for the entire period of study. Intranuclear structures seen in measles-infected hamster nervous tissue were very similar to those observed in SSPE brain biopsy material (5, 18, 24, 26). Budding viral particles have been described in neurons in measles-infected dorsal root ganglion cultures where viral morphogenesis mas observed up to 63 days PI. The purpose of the present study was to maintain measles virus-infected CNS tissue for longer periods and to delineate further the virus-host cell relationships. In addition, the synthesis of virus in CNS tissue was documented. A preliminary rcport of this study was presented at thc 47th annual meeting of tlic American Association of Neuropathologists.