Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Apoptosis induction by the Therien and vaccine RA27/3 strains of rubella virus causes depletion of oligodendrocytes from rat neural cell cultures. 1218 66

The time-course of rubella virus (RV)-induced apoptosis was studied in RK13 cells. DEVD-specific caspase activity assay and Western blotting for caspase-3 were used to determine the time-course of caspase activation and demonstrated that RV-induced apoptotic changes occur as early as 12 h post-infection (p.i.). Caspase activity followed a cyclic pattern, as seen with apoptotic-inducing drugs, with maximum activity detected at 72 h p.i. Apoptosis caused by wild-type (RN) and attenuated vaccine (Cendehill) strains of RV was compared by TUNEL staining, counting dead floating cells and DNA fragmentation analysis. Although the amount of apoptosis due to the wild-type strain was marginally greater, this was probably due to its faster growth rate.
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PMID:Time-course induction of apoptosis by wild-type and attenuated strains of rubella virus. 1269 94

Apoptosis is an important mechanism by which virus-infected cells are eliminated from the host. Accordingly, many viruses have evolved strategies to prevent or delay apoptosis in order to provide a window of opportunity in which virus replication, assembly and egress can take place. Interfering with apoptosis may also be important for establishment and/or maintenance of persistent infections. Whereas large DNA viruses have the luxury of encoding accessory proteins whose primary function is to undermine programmed cell death pathways, it is generally thought that most RNA viruses do not encode these types of proteins. Here we report that the multifunctional capsid protein of Rubella virus is a potent inhibitor of apoptosis. The main mechanism of action was specific for Bax as capsid bound Bax and prevented Bax-induced apoptosis but did not bind Bak nor inhibit Bak-induced apoptosis. Intriguingly, interaction with capsid protein resulted in activation of Bax in the absence of apoptotic stimuli, however, release of cytochrome c from mitochondria and concomitant activation of caspase 3 did not occur. Accordingly, we propose that binding of capsid to Bax induces the formation of hetero-oligomers that are incompetent for pore formation. Importantly, data from reverse genetic studies are consistent with a scenario in which the anti-apoptotic activity of capsid protein is important for virus replication. If so, this would be among the first demonstrations showing that blocking apoptosis is important for replication of an RNA virus. Finally, it is tempting to speculate that other slowly replicating RNA viruses employ similar mechanisms to avoid killing infected cells.
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PMID:The Rubella virus capsid is an anti-apoptotic protein that attenuates the pore-forming ability of Bax. 2137 37

The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness. The additional reduction of stress fibers noted for only some RV strains as the most severe actin rearrangement lowered cell stiffness. Furthermore, a reduced collective and single cell migration speed in a wound healing assay was detected in addition to severe changes in cell morphology. The latter was followed by activation of caspase 3/7 as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a sensitive means to characterize viral cell populations and to implicate alterations of cell mechanical properties with cell functions. These interdependent events are not only promising options to elucidate viral spread and to understand viral pathologies within the infected host. They also contribute to any diseased cell state, as exemplified by RV as a representative agent for cytoskeletal alterations involved in a cytopathological outcome.
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PMID:Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis. 3021 36