MOLECULAR ANALYSIS OF CRITICAL SEQUENCES WITHIN THE EBNA-2 TYPE-1 GENE FROM EPSTEIN-BARR-VIRUS ISOLATES FROM PATIENTS WITH INFECTIOUS-MONONUCLEOSIS, TONSILLAR HYPERPLASIA, AND HIV-INFECTION

EBNA-2 is the first protein to be detected after infection of primary B lymphocytes by Epstein-Barr virus (EBV) and plays an essential role as transcriptional activator in EBV-induced lymphocyte transformation. We analysed by PCR and sequencing regions of the EBNA-2 type 1 gene f rom isolates from 13 children with infectious mononucleosis (IM), 6 ch ildren with tonsillar hyperplasia (TH), and 9 patients with HIV infect ion followed longitudinally. We found in all three groups of patients frequent non-silent point mutations at positions 48990, 48991, 49021, 49057, 49083, 49089, 49091, 49113, 49119, 49140, 49156, and a triplet insertion at position 49136. While 4 out of 13 samples from patients w ith IM showed a mosaic pattern suggesting co-existence of more than 1 substrain of EBNA-2 type I, none of the samples from TH showed this pa ttern consistent with substrain selection during clinical latency. No sequence changes were noted over time in samples derived from patients with HIV infection. We conclude that in analogy to the coexistence of several subtypes of EBNA-1 in healthy EBV carriers, samples from IM c an harbor more than one subtype of the EBNA-2 type 1 gene.