EPSTEIN-BARR VIRAL GENE-EXPRESSION IN B-LYMPHOCYTES

The strategy of the Epstein-Barr virus to persist lifelong in the host depends on establishing a reservoir, which cannot be detected by the immune system but allows reactivation of the virus for shedding and tr ansmission to a new host. Epithelial cells and B-cells play a major ro le in this viral strategy of EBV, since differentiating epithelial tis sues were shown to be permissive for lytic replication in vivo, wherea s the B-lymphocytes become predominantly latently infected. However, w hich cells are the reservoir and which the sites of lytic replication are not quite clear. With the technique of reverse transcription, PCR and immunohistochemistry, we demonstrated that the B-cells of the peri pheral blood are a major site of virus production during the primary i nfection during infectious mononucleosis. These permissive B-cells wer e also detected after convalescence, however, the absence of any lytic transcripts suggested an efficient immunological control very early i n the viral lytic cycle. Serological data on reactivation of EBV corre lated with the detection of lytic cycle transcripts in the blood and t hus demonstrated that the site of virus production during infectious m ononucleosis must be different from that of the persistent state. In t hose cases, where the infection takes a chronic active course, control of lytic replication is insufficient, either on the level of immune s urveillance or of viral gene regulation. We have demonstrated a virus strain with a lytic phenotype in an individual suffering chronic activ e infection. The impaired capability of this virus to immortalise B-ce lls correlated with an enhanced expression of the lytic switch gene BZ LF-1 and downregulation of latent regulatory genes in the early phase of infection.