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Journal of Virology, July 2004, p. 7131-7137, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7131-7137.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Selection Pressure-Driven Evolution of the Epstein-Barr Virus-Encoded Oncogene LMP1 in Virus Isolates from Southeast Asia

Jacqueline M. Burrows,1,{dagger} Lindell Bromham,2,{dagger} Megan Woolfit,2 Gwenaël Piganeau,2 Judy Tellam,1 Geoff Connolly,1 Natasha Webb,1 Leith Poulsen,1 Leanne Cooper,1 Scott R. Burrows,1 Denis J. Moss,1 Sofia M. Haryana,3 Mun Ng,4 John M. Nicholls,4 and Rajiv Khanna1*

Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, The Bancroft Centre, and Joint Oncology Program, Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia,1 Centre for the Study of Evolution, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom ,2 Department of Pathology, University of Hong Kong, Hong Kong SAR, People's Republic of China,3 Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia4

Received 2 December 2003/ Accepted 12 March 2004

The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene, LMP1, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that LMP1 sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.

* Corresponding author. Mailing address: Queensland Institute of Medical Research, Bancroft Centre, 300 Herston Rd., Brisbane, Australia 4029. Phone: 61-7-362 0385. Fax: 61-7-3845 3510. E mail: rajivK{at}qimr.edu.au.

{dagger} These authors contributed equally to this study, and their order should be considered arbitrary.

Journal of Virology, July 2004, p. 7131-7137, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7131-7137.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chow, K.-P. N, Wu, C C, Chang, H Y, Chang, C, Chang, Y S (2008). A simplified tumour model established via Epstein-Barr virus-encoded, nasopharyngeal carcinoma-derived oncogene latent membrane protein 1 in immunocompetent mice. Lab Anim 42: 193-203 [Abstract] [Full Text]  
  • Jansson, A., Johansson, P., Li, S., Rymo, L. (2007). Activity of the LMP1 gene promoter in Epstein-Barr virus-transformed cell lines is modulated by sequence variations in the promoter-proximal CRE site. J. Gen. Virol. 88: 1887-1894 [Abstract] [Full Text]  


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