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Poliovirus induces apoptosis in the human U937 promonocytic cell line
J A López-Guerrero1, M Alonso, F Martín-Belmonte
1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, Madrid, 28049, Spain. jalopez@cbm.uam.es
Abstract:
The human promonocytic U937 cell line, which is moderately susceptible to poliovirus infection, has been used to investigate the induction of apoptosis by this virus. Infection of U937 cells with poliovirus induces morphological changes typical of apoptosis. Poliovirus-resistant U937 cells (PRU) have been isolated that are resistant to apoptosis induced by poliovirus, but that undergo apoptosis after treatment with TNF plus cycloheximide. Despite the fact that poliovirus triggers nitric oxide production in U937 cells, the inhibitor of inducible nitric oxide (NO) synthase, N(omega)-monomethyl-l-arginine, did not hinder apoptosis after infection, suggesting that NO does not play a direct role in this process. Finally, poliovirus infection of U937 cells led to the cleavage of pro-caspase-3 and poly(ADP-ribose)polymerase, indicating the activation of the CPP32 ICE-like cysteine protease in the induction of apoptosis. Our findings suggest that cellular death takes place in U937 cells productively infected by poliovirus as a result of apoptosis and involves caspase activation.
Insights
Poliovirus infection induces apoptosis, a form of programmed cell death, in U937 cells. This process involves caspase activation and is independent of nitric oxide, despite viral induction of its production.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- The human promonocytic U937 cell line is moderately susceptible to poliovirus.
- Understanding virus-induced cell death mechanisms is crucial in virology.
Purpose of the Study:
- To investigate the induction of apoptosis by poliovirus in U937 cells.
- To elucidate the role of nitric oxide and caspases in poliovirus-induced apoptosis.
Main Methods:
- Infection of U937 cells and poliovirus-resistant U937 (PRU) cells with poliovirus.
- Morphological assessment of apoptosis.
- Treatment with nitric oxide synthase inhibitor and TNF plus cycloheximide.
- Western blot analysis for caspase-3 and PARP cleavage.
Main Results:
- Poliovirus infection induced morphological changes indicative of apoptosis in U937 cells.
- PRU cells were resistant to poliovirus-induced apoptosis but sensitive to TNF/cycloheximide.
- Nitric oxide synthase inhibition did not prevent apoptosis.
- Poliovirus infection led to the cleavage of pro-caspase-3 and poly(ADP-ribose)polymerase.
Conclusions:
- Poliovirus infection triggers apoptosis in U937 cells.
- Apoptosis induction involves caspase activation, specifically the CPP32 ICE-like cysteine protease.
- Nitric oxide does not appear to play a direct role in poliovirus-induced apoptosis in this cell line.