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Inhibition of NF-κ B activity and cFLIP expression contribute to viral-induced apoptosis

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Abstract

Virus-induced activation of nuclear factor-kappa B (NF-κB) is required for Type 3 (T3) reovirus-induced apoptosis. We now show that NF-κB is also activated by the prototypic Type 1 reovirus strain Lang (T1L), which induces significantly less apoptosis than T3 viruses, indicating that NF-κB activation alone is not sufficient for apoptosis in reovirus-infected cells. A second phase of virus-induced NF-κB regulation, where NF-κB activation is inhibited at later times following infection with T3 Abney (T3A), is absent in T1L-infected cells. This suggests that inhibition of NF-κB activation at later times post infection also contributes to reovirus-induced apoptosis. Reovirus-induced inhibition of stimulus-induced activation of NF-κB is significantly associated with apoptosis following infection of HEK293 cells with reassortant reoviruses and is determined by the T3 S1 gene segment, which is also the primary determinant of reovirus-induced apoptosis. Inhibition of stimulus-induced activation of NF-κB also occurs following infection of primary cardiac myocytes with apoptotic (8B) but not non-apoptotic (T1L) reoviruses. Expression levels of the NF-κB-regulated cellular FLICE inhibitory protein (cFLIP) reflect NF-κB activation in reovirus-infected cells. Further, inhibition of NF-κB activity and cFLIP expression promote T1L-induced apoptosis. These results demonstrate that inhibition of stimulus-induced activation of NF-κB and the resulting decrease in cFLIP expression promote reovirus-induced apoptosis.

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Authors and Affiliations

  1. Departments of Neurology, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA

    P. Clarke, R. L. DeBiasi, S. M. Meintzer, B. A. Robinson & K. L. Tyler

  2. Department of Neurology (B 182), University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA

    P. Clarke

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Clarke, P., DeBiasi, R.L., Meintzer, S.M. et al. Inhibition of NF-κ B activity and cFLIP expression contribute to viral-induced apoptosis. Apoptosis 10, 513–524 (2005). https://doi.org/10.1007/s10495-005-1881-4

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