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Apoptosis induction by the Therien and vaccine RA27/3 strains of rubella virus causes depletion of oligodendrocytes from rat neural cell cultures

Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland¹

Author for correspondence: Greg Atkins. Fax +353 1 6799294. e-mail gatkins{at}tcd.ie

The induction of cell death by the Therien strain of rubella virus (RVT), and the vaccine RA27/3 strain, was investigated in mixed glial cell cultures derived from the rat CNS. Cell death induction in Vero and rat glial cells by RVT and RA27/3 was dependent on virus replication. In both cell types and for both virus strains, cell death induction had the hallmarks of apoptosis, as detected by DNA laddering, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling staining and Annexin V staining. For rat mixed glial cells, the depletion of oligodendrocytes was due to the induction of apoptosis for both virus strains. The induction of apoptosis in H358a cells, which carry a homozygous deletion of the p53 gene, indicated that a p53-independent pathway can be involved. The induction of cell death by RVT and RA27/3 in Vero and rat glial cells was associated with caspase-3 activity. It is concluded that rubella virus (RV) induces apoptosis in oligodendrocytes in rat glial cell cultures by a caspase-dependent pathway and that similar mechanisms occur for both the RVT laboratory strain and the vaccine RA27/3 strain. The tropism of both strains of RV for oligodendrocytes and the induction of apoptosis in such cells may have important implications for the mechanism of virus neuropathogenesis.

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