J K Chantler1, L Smyrnis, G Tai. 1. Department of Pathology, University of British Columbia, Vancouver, Canada.
Abstract
BACKGROUND: Rubella virus (RV) can cause a wide variety of neurologic symptoms, particularly when infection occurs in utero. However, little is known about the pathogenesis of these infections and the cell types in human brain susceptible to infection have not been characterized. EXPERIMENTAL DESIGN: Cell cultures derived from human brain tissue were examined for susceptibility to two wild-type and two vaccine strains of RV. Cell types expressing viral antigen were identified by double-label immunofluorescence with monoclonal antibodies to specific cell markers and a polyclonal anti-RV antibody. Viral yield was determined by plaque assay. RESULTS: All four RV strains replicated in the brain cultures, although the titers obtained in the case of the vaccine strains were more than 100-fold lower than those found for wild-type isolates. Astrocytes appeared to be the main cell type infected, expressing large amounts of viral antigen. In contrast, oligodendrocytes were rarely productively infected, even when surrounded by infected astrocytes. Occasional neurons expressing viral antigen were also seen. CONCLUSIONS: The main cell type permissive to RV infection in developing brain tissue is the astrocyte. Although not highly cytolytic, the virus may disrupt the functioning of these cells, resulting in neurologic deficits. The restricted replication of this virus in oligodendrocytes correlates with the lack of demyelination generally reported as being typical of RV neurologic disease.
BACKGROUND:Rubella virus (RV) can cause a wide variety of neurologic symptoms, particularly when infection occurs in utero. However, little is known about the pathogenesis of these infections and the cell types in human brain susceptible to infection have not been characterized. EXPERIMENTAL DESIGN: Cell cultures derived from human brain tissue were examined for susceptibility to two wild-type and two vaccine strains of RV. Cell types expressing viral antigen were identified by double-label immunofluorescence with monoclonal antibodies to specific cell markers and a polyclonal anti-RV antibody. Viral yield was determined by plaque assay. RESULTS: All four RV strains replicated in the brain cultures, although the titers obtained in the case of the vaccine strains were more than 100-fold lower than those found for wild-type isolates. Astrocytes appeared to be the main cell type infected, expressing large amounts of viral antigen. In contrast, oligodendrocytes were rarely productively infected, even when surrounded by infected astrocytes. Occasional neurons expressing viral antigen were also seen. CONCLUSIONS: The main cell type permissive to RV infection in developing brain tissue is the astrocyte. Although not highly cytolytic, the virus may disrupt the functioning of these cells, resulting in neurologic deficits. The restricted replication of this virus in oligodendrocytes correlates with the lack of demyelination generally reported as being typical of RV neurologic disease.