SEQUENCE VARIATIONS IN EBNA-1 MAY DICTATE RESTRICTION OF TISSUE DISTRIBUTION OF EPSTEIN-BARR-VIRUS IN NORMAL AND TUMOR-CELLS

In seropositive individuals Epstein-Barr virus (EBV) establishes a vir us reservoir in peripheral blood lymphocytes (PBLs). Transmission from one individual to another occurs via saliva due to a lytic (virion pr oductive) phase of infection in the oropharynx. EBNA-1 is responsible for maintaining viral episomes in the host cell and could, therefore, also affect the persistence of the virus in different cell lineages. B ased on sequence analysis of EBNA-1 we now demonstrate that (i) in add ition to the prototype EBNA-1 (identical to the B95.8 virus EBNA-1), E BV in normal individuals encompasses multiple EBNA-1 subtypes, both in PBLs and in oral secretions; (ii) although EBV with prototype EBNA-1 is the predominant virus in normal individuals, it is very rarely asso ciated with either nasopharyngeal carcinoma (NPC) or Burkitt's lymphom a (BL); (iii) EBV with an EBNA-1 subtype (V-val) frequently associated with NPC is also selectively detected in oral secretions and not in P BLs; (iv) EBV with the EBNA-1 subtype V-pro is restricted to PBLs, whi le a mutated version of this subtype is present in BL, but not in NPC. These findings suggest that the variations in EBNA-1 may be relevant to the ability of EBV to persist in different cell types, and hence re levant to its oncogenic potential.