Epstein-Barr Virus LMP-1 Natural Sequence Variants Differ in Their Potential To Activate Cellular Signaling Pathways

Abstract

The latent membrane protein 1 (LMP-1) oncogene of Epstein-Barr virus (EBV) is believed to contribute to the development of many EBV-associated tumors, and there is evidence that sequence variation can affect some functions of LMP-1. Most studies have been restricted to the prototype B95.

Multiple signal transducers and activators of transcription are induced by EBV LMP-1

“…Latent nonphosphorylated STAT-1 is able to move into the nucleus, bind to DNA, and is responsible for the constitutive expression of LMP-2 (Chatterjee- Kishore et al, 2000). Also, LMP-1 has been reported to activate a STATresponsive element (Fielding et al, 2001;Richardson et al, 2003); the induction of STAT-1, -2, and -3 could possibly explain that observation (Figure 4).…”

“…However, whether JAK3 can bind to these sites and is responsible for the activation of signal transducer and activator of transcription 1 (STAT-1) or other STATs is controversial Fielding et al, 2001;Gires et al, 1999;Higuchi et al, 2002).…”

Epstein–Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells

“…LMP1 natural sequence variants differ in their potential to activate cellular signaling pathways (Fielding et al, 2001). We then compared the ability of two LMP1 variants, 2117-LMP1 and B95.8-LMP1, to induce the Id1 expression and activate NF-kB signaling.…”

Induction of inducible nitric oxide synthase by Epstein-Barr virus B95-8-derived LMP1 in Balb/3T3 cells promotes stress-induced cell death and impairs LMP1-mediated transformation

“…It is known that NLMP1 is more oncogenic than BLMP1 (Chen et al, 1992;Hu et al, 1993;Li et al, 1996) and less immunogenic (Trivedi et al, 1994). Furthermore, although both BLMP1 and NPC-derived LMP1 activate transcription factors, NFkB and AP-1, it appears that NLMP1 functions more efficiently in Jurkat cells (Fielding et al, 2001), but not C33A cells (Yeh et al, 1997). Additional reports demonstrate that the expression levels of several cell surface molecules (CD40, CD44, and CD54), interleukins-6 and -8, and epidermal growth factor receptor differ between BLMP1-and NLMP1-expressing cells (Johnson et al, 1998;Miller et al, 1998;Dawson et al, 2000).…”