Fielding, Ceri Alan  ORCID: https://orcid.org/0000-0002-5817-3153, Sandvej, Kristian, Mehl, Anja Maria, Brennan, Paul ORCID: https://orcid.org/0000-0001-8792-0499, Jones, Matthew and Rowe, Martin
2001.
Epstein-Barr virus LMP-1 natural sequence variants differ in their potential to activate cellular signaling pathways.
Journal of Virology
75
(19)
, pp. 9129-9141.
10.1128/JVI.75.19.9129-9141.2001
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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 B95.8 LMP-1 gene and genes isolated from EBV of nasopharyngeal carcinoma (NPC) patients. Here, we analyzed the signaling functions of LMP-1 from a panel of nine EBV isolates, including representatives of four defined groups of European LMP-1 variants (groups A to D [K. Sandvej, J. W. Gratama, M. Munch, X. G. Zhou, R. L. Bolhuis, B. S. Andresen, N. Gregersen, and S. Hamilton-Dutoit, Blood 90:323-330, 1997]) and Chinese NPC-derived LMP-1. Chinese and group D variants activated the transcription factor NF-kappa B two- to threefold more efficiently than B95.8 LMP-1, while Chinese, group B, and group D variants similarly activated activator protein 1 (AP-1) transcription more efficiently than did B95.8 LMP-1. However, there were no amino acid substitutions in the core binding regions for tumor necrosis factor receptor-associated adapter proteins known to mediate NF-kappa B and AP-1 activation. In contrast, despite sequence variation in the proposed Janus kinase 3 binding region, STAT activation was remarkably constant among the panel of LMP-1 variants. Analysis of the induction of CD54 (intercellular adhesion molecule 1) protein expression by the LMP-1 variants showed differences that did not correlate with either NF-kappa B or AP-1. Therefore, while the defined sequence variant groups do correlate with LMP-1 function, the results highlight the fact that the relationship between sequence variation and signaling function is extremely complex. It appears unlikely that one particular amino acid substitution or deletion will define a disease-associated variant of LMP-1.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Additional Information: | Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014) |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| Date of First Compliant Deposit: | 30 March 2016 |
| Last Modified: | 09 May 2023 20:51 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/232 |
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