Epstein-Barr virus nuclear antigen 1 sequences in endemic and sporadic Burkitt's lymphoma reflect virus strains prevalent in different geographic areas

Epstein-Barr virus (EBV) nuclear antigen EBNA1 is the only viral protein de tectably expressed in virus genome-positive Burkitt's lymphoma (BL); recent work has suggested that viral strains with particular EBNA1 sequence chang es are preferentially associated with this tumor and that, within a patient , the tumor-associated variant may have arisen de novo as a rare mutant of the dominant preexisting EBV strain (K. Bhatia, A. Raj, M. J. Gutierrez, J. G. Judde, G. Spangler, H. Venkatesh, and I. T. Magrath, Oncogene 13:177-18 1, 1996). In the present work we first study 12 BL patients and show that t he virus strain in the tumor is identical in EBNA1 sequence and that it is matched at several other polymorphic loci to the dominant strain rescued in vitro from the patient's normal circulating B cells. We then analyze BL-as sociated virus strains from three different geographic areas (East Africa, Europe, and New Guinea) alongside virus isolates from geographically matche d control donors by using sequence changes in two separate regions of the E BNA1 gene (N-terminal codons 1 to 60 and C-terminal codons 460 to 510) to i dentify the EBNA1 subtype of each virus. Different geographic areas display ed different spectra of EBNA1 subtypes, with only limited overlap between t hem; even type 2 virus strains, which tended to be more homogeneous than th eir type 1 counterparts, showed geographic differences at the EBNA1 locus. Most importantly, within any one area the EBNA1 subtypes associated with BL were also found to be prevalent in the general population. We therefore fi nd no evidence that Burkitt lymphomagenesis involves a selection for EBV st rains with particular EBNA1 sequence changes.