Mammalian reoviruses are important models for studies of viral infections of the nervous system. These viruses are non-enveloped, RNA-containing viruses that replicate in the cytoplasm of infected cells. Reoviruses induce apoptosis as an important component of their cytopathic effect both in cultured cells and in the murine central nervous system. Differences in the capacity of reovirus strains to induce apoptosis are determined by the receptor-binding protein, and reovirus virions inactivated by UV irradiation retain the capacity to trigger apoptosis. These findings suggest that reovirus-induced apoptosis is triggered by a signal-transduction cascade initiated by viral attachment to the cell surface. To identify components of the cell-signaling apparatus required for apoptosis induction by reovirus, we investigated whether reovirus infection activates NF-κB, a transcription factor linked to apoptosis in many cell types. Reovirus infection of MDCK epithelial cells induces nuclear translocation of NF-κB as assessed by electrophoretic mobility shift assays using nuclear extracts from infected cells and oligonucleotide probes containing NF-κB-binding sequences. MDCK cells engineered to express a trans-dominant inhibitor of IκB, which prevents nuclear translocation of NF-κB, exhibit a block to apoptosis induced by reovirus infection. These findings indicate that reovirus-induced apoptosis requires activation of NF-κB, which establishes a new paradigm for the interaction of RNA-containing viruses with critical cell-signaling pathways.
|Original language||English (US)|
|Number of pages||1|
|Journal||Clinical Infectious Diseases|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases