NF-κB is essential for the progression of KSHV- and EBV-infected lymphomas in vivo

Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

“…Consistent with persistent activation of NF-kB being involved in HHV-8-associated disease, inhibition of NF-kB induces apoptosis in PEL cells (Keller et al, 2006), and as with EBV-infected cells, this appears to be due to downregulation of NF-kB-dependent survival genes such as IAP, cFLIP and IL-6 (Keller et al, 2006). Moreover, inhibition of NF-kB by expression of the IkBa superrepressor blocks the production of infectious HHV-8 virions (Sgarbanti et al, 2004), demonstrating the importance of NF-kB activation in both latent and lytic infection.…”

“…LMP-1 activates NF-kB (Herrero et al, 1995;Cahir-McFarland et al, 2000), mainly via effects on the NF-kB subunit c-Rel (Thornburg et al, 2005). (Laherty et al, 1992) and prosurvival genes including IAPs, c-FLIP and IL-6 (Keller et al, 2006). NF-kB activation also mediates many of the phenotypic effects of LMP-1, including the upregulation of ICAM-1, LFA-3, CD40, IL-6, Fas, TRAF1, EBI3 and cyclooxygenase-2, typical of EBV-induced transformation.…”

CTLA-4 · FasL Induces Early Apoptosis of Activated T Cells by Interfering with Anti-Apoptotic Signals

“…cFLIP has been associated with T cell responses to TCR stimulation (45), and when cFLIP is over-expressed, Fas ligation induces proproliferative signals mediated by NF-B (42)(43)(44)46). Furthermore, inhibition of the NF-B pathway effectively inhibits vFLIP-induced lymphocyte proliferation in Kaposi sarcoma virus-infected lymphomas (17). Thus, his 6 CTLA-4 ⅐ FasL-driven down-regulation of cFLIPs at an early stage may both favor apoptosis and also coordinately prevent proliferation, the latter by inhibiting the NF-B pathway.…”

“…ϩ APC surface membranes, it is in effect generating FasL ϩ deletional APC, or "artificial veto cells" (17). Genetically engineered APC expressing FasL can clonally delete activated Fas-bearing T cells that recognize cognate Ags on these APC (18).…”

Current insights into the regulation of programmed cell death by NF-κB

“…As transgenic mice expressing v-FLIP remain sensitive to Fas-mediated apoptosis, the role of v-FLIP in oncogenesis was suggested to be independent of inhibition of Fas-mediated killing (Chugh et al, 2005). Thus, activation of NF-kB appears to be a critical mechanism by which EBV-and KHSV-infected lymphoma cells are spared from apoptosis and inhibition of NF-kB is associated with downregulation of various antiapoptotic targets (Keller et al, 2006).…”