Balkan Journal of Medical Genetics

NOVEL PATTERNS OF THE EPSTEIN-BARR NUCLEAR ANTIGEN (EBNA-1) V-VAL SUBTYPE IN EBV-ASSOCIATED NASOPHARYNGEAL CARCINOMA FROM VIETNAM
Thuan LD1, Kha ND2, Minh NT3, Thuy LHA1,*
*Corresponding Author: Thuy Le Huyen Ai, Ph.D., Associate Professor, Department of Pharmaceutical and Medical Biotechnology, Faculty of Biotechnology, Room 304, 97 Vo Van Tan Street, Ward 6, District 3, Ho Chi Minh City Open University, Ho Chi Minh City, Vietnam. Tel: +84-905-784-471. E-mail: thuy.lha@ ou.edu.vn
page: 61

INTRODUCTION

Epstein-Barr virus (EBV), a ubiquitous human gramma herpes virus, discovered in 1964 by Epstein and Barr, taxonomically identified as human herpes virus 4, is an oncogenic virus causing many EBV-associated human malignancies, including Hodgkin’s disease, gastric carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma (NPC) [1-5]. Following the infection of EBV, it remains in two stages: latency, lytic or productive phase of the life cycle of EBV [6]. Many processes of the viral cycle was dependent on the Epstein-Barr nuclear antigen (EBNA-1). Epstein-Barr nuclear antigen 1, a 641 amino acid protein, is the only consistently detected viral protein in many human EBV-associated malignancies [3,7,8]. Epstein-Barr nuclear antigen 1 is essential for EBV immortalization, the maintenance, replication and transcription of EBV genome, segregate EBV episome at mitosis [4,9]. A high frequency of sequence substitutions was identified in the carboxyl terminal (residues 325-641) of EBNA-1, containing many functional domains: the dimerization domain (residues 501- 532 and 554-598), DNA binding domain (residues 459- 487) and the transactivation domain (residues 450-641) [8,10-12]. Sequence variants occurring at the C-terminal of EBNA-1 may affect the functions of EBNA-1 protein, and consequently, affect DNA replication, transcription, or oncogenic potential EBV [9,13]. The sequence substitutions were frequently identified between residue 487 and 583 [14]. The two main mutant groups were identified and termed as prototype strains (similar to the prototype isolated from B95 cell line) and variant strains, which differed by 15 amino acids [14]. The further subtype identification was based on the amino acid at position 487 [14,15]. The EBV isolates could be divided into five subtypes: there are two prototype strains (P-strain) with either an alanine residue (termed as P-Ala), or a threonine residue (termed as P-Thr) at position 487, and three variant strains (V-strain) with either a leucine residue (termed as V-Leu), a valine residue (termed as V-Val) or a proline residue (termed as V-Pro) at this position [14,15]. These EBNA-1 subtypes display an association with geographical and human disease distribution. In these, V-Val is more frequent in NPC and almost detected in Chinese population, and preferentially exists in biopsies of NPC [15,16]. Vietnam, located in Southern Asia, is well known for the high incidence and mortality rate of NPC in the world [17]. However, most studies on EBNA-1 subtype classification were limited to NPC in the Chinese, not in Vietnamese population. In our previous study, we established the protocol for genotyping of the EBNA-1 subtype from of nasopharyngeal biopsy samples collected from Vietnamese NPC patients, and the results suggested that the V-Val subtype is the preferentially subtype associated with NPC [18]. In this current study, in order to explore the characteristics of the V-Val subtype in the Vietnamese population, we analyzed the polymorphisms of the EBNA-1 gene in EBV-associated NPC in the comparison to the prototype B95-8 strain.

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