Epstein-Barr Virus Gene Expression in the Peripheral Blood of Transplant Recipients with Persistent Circulating Virus Loads

Pediatric solid organ transplant recipients are at risk for Epstein-Barr virus (EBV)-driven lymphoproliferative disease. The expression of 5 sentinel EBV genes (EBNA1, EBNA2a, LMP1, LMP2a, and ZEBRA) was examined in solid organ transplant recipients who developed persistent virus loads in their peripheral blood lymphocytes after transplantation. Two distinct groups were identified. LMP2a gene expression alone was detected among 12 of 14 patients carrying EBV loads ≤100 copies/10 5 lymphocytes. The other 2 low-load carriers made LMP2a RNA but also expressed LMP1 RNA. In contrast, LMP2a and LMPI gene expression was detected among 11 of 13 patients carrying a virus load >100 copies/10 5 lymphocytes. Two high-load carriers made LMPI RNA but not the RNA for LMP2a or any of the other viral genes. Therefore, persistent low-load carriers appear to maintain an apparently normal state of latent viral infection, whereas high-load carriers display a unique LMP1:LMP2a pattern of viral gene expression that has not been previously described.