Sequence variations in EBNA-1 may dictate restriction of tissue distribution of Epstein-Barr virus in normal and tumour cells.
In seropositive individuals Epstein-Barr virus (EBV) establishes a virus reservoir in peripheral blood lymphocytes (PBLs). Transmission from one individual to another occurs via saliva due to a lytic (virion productive) 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. Based on sequence analysis of EBNA-1 we now demonstrate that (i) in addition to the prototype EBNA-1 (identical to the B95.8 virus EBNA-1), EBV 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 associated with either nasopharyngeal carcinoma (NPC) or Burkitt's lymphoma (BL); (iii) EBV with an EBNA-1 subtype (V-val) frequently associated with NPC is also selectively detected in oral secretions and not in PBLs; (iv) EBV with the EBNA-1 subtype V-pro is restricted to PBLs, while 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 relevant to its oncogenic potential.
Gutiérrez
M I
MI
Lymphoma Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA.
Raj
A
A
Spangler
G
G
Sharma
A
A
Hussain
A
A
Judde
J G
JG
Tsao
S W
SW
Yuen
P W
PW
Joab
I
I
Magrath
I T
IT
Bhatia
K
K
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000821:virology; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D012463:Saliva / Q000821:virology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D019309:Epstein-Barr Virus Nuclear Antigens