DETECTION OF MULTIPLE EPSTEIN-BARR VIRAL STRAINS IN ALLOGENEIC BONE-MARROW TRANSPLANT RECIPIENTS

We have previously shown in 3 allogeneic bone-marrow transplant (BMT) recipients that complete replacement of recipient marrow was associated with the elimination of the pretransplant Epstein-Barr virus (EBV) strain of the recipient. To study the kinetics of EBV elimination and reinfection in more detail, we have performed a longitudinal study of BMT recipients combining serology, virus isolation from mouthwashes and peripheral blood, and EBV strain characterization. Oropharyngeal EBV excretion was found to persist after the cytoreductive therapy prior to BMT, whereas EBV-carrying cells in the blood were detected only after 5 weeks following BMT. During the first month post-BMT, 2 different EBV strains could be isolated from sequential mouthwashes of 3 patients. The initial strains were found to persist up to 7, 21, and 29 days post-BMT, whereas the subsequent strains appeared at 21, 42, and 34 days post-BMT, respectively. Thus, the original EBV strain may persist only for a limited time after BMT, and the oropharyngeal epithelium may be reinfected by a new EBV strain from the blood within 3 weeks. With respect to the coexistence of multiple EBV strains, 2 patterns were evident. From the day 62 mouthwash of 1 patient, 1 Type A and 1 Type B strain were isolated. From the day 180 mouthwash of a second patient, a dominant Type A strain was recovered, together with 6 "variant" strains that differed from each other by only a single EBNA protein (EBNA 1). This pattern may be explained by viral recombinations during replication, which may form the basis for the vast polymorphism of EBV observed in unrelated individuals.