Key Points
- To investigate the mechanisms by which poliovirus nonstructural proteins modulate host cell sensitivity to tumor necrosis factor (TNF)-induced extrinsic apoptosis.
- Assessed host cell apoptotic responses and downstream signaling pathways upon expression of poliovirus nonstructural proteins 2A, 2B, and 3A.
- Measured cell-surface TNF receptor abundance postinfection and compared receptor trafficking disruption to treatment with brefeldin A.
- Viral proteinase 2A increases sensitivity to TNF-induced apoptosis, whereas nonstructural proteins 3A and 2B induce strong resistance to TNF.
- Expression of protein 3A suppresses NF-kappaB activation and neutralizes 2A activity by eliminating TNF receptors from the cell surface within 4 hours postinfection via disruption of endoplasmic reticulum-Golgi trafficking.
Structured PICO
PPopulationCells (in vitro model)
IInterventionExpression of poliovirus noncapsid proteins 3A and 2B or poliovirus infection
OOutcomeSensitivity to tumor necrosis factor (TNF)-induced apoptosis and TNF receptor abundance on the cell surfacesurrogate
Poliovirus protein 3A confers resistance to TNF-induced apoptosis by interfering with endoplasmic reticulum-Golgi protein trafficking, leading to aberrant TNF receptor trafficking and elimination from the cell surface.