Transforming Growth Factor Beta 1 Stimulates Expression of the Epstein-Barr Virus BZLF1 Immediate-Early Gene Product ZEBRA by an Indirect Mechanism Which Requires the MAPK Kinase Pathway

Abstract

Disruption of Epstein-Barr virus (EBV) latency is mediated by

Radiation-induced Epstein–Barr virus reactivation in gastric cancer cells with latent EBV infection

“…21 In a more recent study, which used another Burkitt lymphoma cell line (Raji), purified recombinant TGFbeta1, added to the culture medium, induced EBV reactivation through cFos and cJun which were upregulated by the mitogen-activated protein kinase (MAPK) pathway. 30 The study also showed that TGF-beta1 upregulated MAPK pathway through a transcription factor Smad3/4. A later study confirmed the involvement of this transcription factor in addition to cFos and cJun in the EBV reactivation induced by TGF-beta1.…”

Activation of the ERK signal transduction pathway by Epstein–Barr virus immediate-early protein Rta

“…7b), implying that, unlike the full-length Rta, these two Rta fragments are not involved in activating the p38 and JNK signalling pathway to activate BZLF1 transcription. Previous studies have demonstrated that activation of ERK signal transduction by TPA, anti-IgG and TGF-b1 is crucial to activation of BZLF1 transcription and the EBV lytic cycle (Fahmi et al, 2000;Fenton & Sinclair, 1999;Satoh et al, 1999). The fact that U0126 reduced the capacity of Rta to activate expression of Zta and EA-D (Fig.…”

“…Previous studies have established that BZLF1 transcription is closely associated with activation of the ERK signal transduction cascade (Fahmi et al, 2000;Fenton & Sinclair, 1999;Satoh et al, 1999). To determine whether Rta activates BZLF1 transcription via the ERK signal transduction pathway, pCMV-R and a BZLF1 reporter plasmid, pZp-Luc, were co-transfected into 293T cells.…”

“…Although the exact means by which the EBV lytic cycle is activated in vivo is unknown, activation in vitro occurs after latently infected cells are exposed to 12-Otetradecanoylphorbol-13-acetate (TPA), calcium ionophores, transforming growth factor (TGF)-b1 or anti-IgG (Daibata et al, 1990; Faggioni et al, 1986;zur Hausen et al, 1978). TPA, anti-IgG and TGF-b1 are known to activate the ERK signal transduction pathway (Fahmi et al, 2000;Fenton & Sinclair, 1999;Gao et al, 2001;Satoh et al, 1999), which ultimately activates transcription of BZLF1 and the EBV lytic cycle (Borras et al, 1996;Flemington & Speck, 1990).It is known that EBV must express Zta to activate its lytic genes (Chevallier-Greco et al, 1986;Chiu et al, 2007;Feederle et al, 2000). Earlier studies have established that Rta upregulates transcription of the Zta gene, BZLF1 (Adamson et al, 2000;Ragoczy et al, 1998;Zalani et al, 1996).…”

Heterogeneous Epstein–Barr virus latent gene expression in AIDS-associated lymphomas and in type I Burkitt's lymphoma cell lines

“…Western blots were performed using anti-EBNA-3B (Exalpha Biologicals) and the A10 anti-EBNA-3C (Radkov et al, 1997), as described previously (Fahmi et al, 2000).…”