Premium
EBNA‐1 sequence variations reflect active EBV replication and disease status or quiescentlatency in lymphocytes
Author(s) -
Wang JiinTarng,
Sheeng TzungShiahn,
Su IhJen,
Chen JenYang,
Chen MeiRu
Publication year - 2003
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10305
Subject(s) - nasopharyngeal carcinoma , mononucleosis , biology , virology , tropism , virus , lymphoma , epstein–barr virus , immunology , population , tissue tropism , gammaherpesvirinae , dna , viral disease , herpesviridae , genetics , medicine , environmental health , radiation therapy
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. J. Med. Virol. 69:417–425, 2003. © 2003 Wiley‐Liss, Inc.