PATHOGENESIS OF CHRONIC EPSTEIN-BARR-VIRUS INFECTION - DETECTION OF AVIRUS-STRAIN WITH A HIGH-RATE OF LYTIC REPLICATION

In rare cases Epstein-Barr virus (EBV) leads to chronic active infecti on (CAEBV) which is characterized by persistant symptoms of infectious mononucleosis. Previously we described a case of persisting polyclona l B-cell lymphocytosis (PPBL) that was associated with CAEBV. Using re verse transcription and polymerase chain reaction we showed that in la te passages of a spontaneous cell line, SM, latent EB viral genes such as EBNA1, EBNA2, EBNA3A/3B/3C, LMP1 and LMP2A were active. The master gene of the lytic cycle, BZLF1, was silent. This indicated that there was no general defect in immortalization and establishing latency by this CAEBV isolate SM. We obtained virus from the standard immortalizi ng strain B95-8 and the CAEBV strain SM from latently infected LCL, qu antified the number of virus particles by competitive PCR and demonstr ated that the impaired capacity to immortalize umbilical cord blood ly mphocytes was a virus strain-specific property, and was not due to an incapability to infect purified CD19(+) B lymphocytes. Transcription o f latency- and immortalization-associated genes such as EBNA1, EBNA2 a nd LMP2A was reduced, in contrast to a strongly enhanced activity of t he master gene of the lytic cycle, BZLF1. A scenario for an antagonist ic regulation of lytic and latent cycle genes is presented and a role for the pathogenesis of CAEBV is discussed.