title: EBNA-1 sequence variations reflect active EBV replication and disease status or quiescent latency in lymphocytes.
abstract: EBV infects most of the global population, but only a small percentage of infected individuals develop EBV-associated malignancies. Host and viral factors may play a role in determining the clinical outcome. Because EBNA-1 functions as an oriP binding protein and links the episomal viral DNA to metaphase chromosomes, variation of EBNA-1 has been suggested to contribute to determining the tissue tropism of EBV and the development of various EBV-associated diseases. Five subtypes have been described, according to the amino acid at residue 487: P-ala (B95-8 prototype), P-thr (aa 487 ala to thr), V-val, V-pro and V-leu. Other studies, however, concluded that EBNA-1 sequence variation simply reflects the geographical distribution of EBV. To clarify these possibilities, we collected DNA samples from healthy individuals and patients with various EBV-associated diseases in Taiwan for PCR amplification and DNA sequencing. The results indicate that: 1) V-val EBNA-1 was detected in patients with nasopharyngeal carcinoma (NPC) and other EBV-associated malignant diseases; 2) the prototype P-ala strain was detected only in peripheral blood lymphocytes; 3) mixed populations of different subtypes of N-terminal and C-terminal sequences were observed in samples from one patient with nasopharyngeal carcinoma, one with T lymphoma and one with infectious mononucleosis sample; 4) intermediate variations between P-ala and V-val were observed in T-lymphoma, Hodgkin disease and infectious mononucleosis samples; and 5) in comparison with the major sequences identified in healthy carriers, the EBNA-1 sequences in peripheral lymphocytes from nasopharyngeal carcinoma were mixed types in 4 of 5 patients, implying increasing frequency of V-val might correlate with the progression of nasopharyngeal carcinoma.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Wang
authors.forename: Tzung-Shiahn
authors.initials: TS
authors.lastname: Sheeng
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Mei-Ru
authors.initials: MR
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002277:Carcinoma / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry* / Q000235:genetics; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000821:virology; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000821:virology; D017422:Sequence Analysis, DNA; D014775:Virus Activation; D017735:Virus Latency / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1