Rubella virus-induced cytopathic effect in vitro is caused by apoptosis

Rubella virus (RV) generally causes a mild disease but it is highly teratogenic when infection occurs during the first trimester of gestation. Under in vitro conditions, RV induces characteristic cytopathic changes on several cell lines, e.g. cell detachment from the monolayer and condensation of chromatin. The purpose of this study was to characterize RV-induced cell death and to determine the factors that might be involved in this process. Both acutely and persistently infected cells exhibited alterations characteristic of apoptosis, including DNA fragmentation, annexin V staining and reduced DNA content. UV-inactivated RV did not induce apoptotic cell death and expression of RV structural proteins in a transfected cell line was not sufficient to induce apoptosis, supporting the interpretation that replicating virus is necessary to provoke apoptosis. Both persistently infected and 24S-transfected cells retained their susceptibility to undergo apoptosis in response to either staurosporine or camptothecin. This indicates that RV does not block chemically induced apoptosis. The signals involved in RV-associated apoptosis appear to be independent of p53 and of the Bcl-2 gene family.