This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Houali, K. Articles by Ooka, T. Search for Related Content PubMed PubMed Citation Articles by Houali, K. Articles by Ooka, T.

A New Diagnostic Marker for Secreted Epstein-Barr Virus–Encoded LMP1 and BARF1 Oncoproteins in the Serum and Saliva of Patients with Nasopharyngeal Carcinoma

Authors' Affiliations: ¹ Laboratoire de Virologie Moléculaire, UMR5537, Centre National de la Recherche Scientifique, Faculté de Médecine Laennec, Université Lyon-1, Lyon Cedex, France; ² Service d'ORL, Hopital Mustapha, Algiers, Algeria; ³ Department of Pathology, University of Hong Kong, Pok Fu Lam, Hong Kong; and ⁴ Institut Pasteur d'Algérie, Sidi-Fredj, Staoueli, Algeria

Requests for reprints: Tadamasa Ooka, Laboratoire de Virologie Moléculaire, UMR5537, CNRS, Faculté de Médecine Laennec, Université Lyon 1, F-69372, Lyon Cedex 08, France. Phone: 33-47801-1836; Fax: 33-47874-9668; E-mail: ooka{at}sante.univ-lyon1.fr.

Purpose: EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodal—the first peak occurring at 20 years of age and the second peak occurring at 50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients. We are interested in two EBV-encoded oncoproteins, LMP1 and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC.

Experimental Design: LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity.

Results: Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1 was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells.

Conclusion: Both proteins will be a good diagnostic marker for NPC whereas BARF1 is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC.

This article has been cited by other articles:

				J.-R. Hsiao, K.-C. Chang, C.-W. Chen, S.-Y. Wu, I.-J. Su, M.-C. Hsu, Y.-T. Jin, S.-T. Tsai, K. Takada, and Y. Chang Endoplasmic Reticulum Stress Triggers XBP-1-Mediated Up-regulation of an EBV Oncoprotein in Nasopharyngeal Carcinoma Cancer Res., May 15, 2009; 69(10): 4461 - 4467. [Abstract] [Full Text] [PDF]

				J. Klibi, T. Niki, A. Riedel, C. Pioche-Durieu, S. Souquere, E. Rubinstein, S. L. E. Moulec, J. Guigay, M. Hirashima, F. Guemira, et al. Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells Blood, February 26, 2009; 113(9): 1957 - 1966. [Abstract] [Full Text] [PDF]

				M. L. Gulley and W. Tang Laboratory Assays for Epstein-Barr Virus-Related Disease J. Mol. Diagn., July 1, 2008; 10(4): 279 - 292. [Abstract] [Full Text] [PDF]

				E. Seto, T. Ooka, J. Middeldorp, and K. Takada Reconstitution of Nasopharyngeal Carcinoma-Type EBV Infection Induces Tumorigenicity Cancer Res., February 15, 2008; 68(4): 1030 - 1036. [Abstract] [Full Text] [PDF]