Banko Ana V, Lazarevic Ivana B, Karalic Danijela Z, Djukic Vojko B, Cupic Maja D, Stevanovic Goran, Jovanovic Tanja P
Virology Department, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica, Belgrade, 11000, Serbia.
Clinic of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Med Microbiol Immunol. 2019 Feb;208(1):81-88. doi: 10.1007/s00430-018-0561-2. Epub 2018 Sep 10.
Epstein-Barr virus (EBV) has been identified as a group 1 carcinogenic agent, particularly for nasopharyngeal carcinoma (NPC). The sequence diversity of EBV nuclear antigen 1 (EBNA1) reflects region-restricted polymorphisms, which may be associated with the development of certain malignancies. The aims of the present study were to evaluate EBV EBNA1 gene polymorphisms circulating in NPC, infectious mononucleosis, and isolates from patients with transplanted organs to determine if EBNA1 sequence specificities are useful as viral biomarkers for NPC. Forty biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), 31 plasma samples from patients with mononucleosis syndrome, and 16 plasma samples from patients after renal transplantation were tested in this study. The EBNA1 gene was amplified by nested PCR. Further investigation included sequencing, phylogenetic, and statistical evaluations. Eighty-seven sequences were identified as one of the four EBNA1 subtypes, P-Ala, P-Thr, V-Val, and V-Ala, with further classification into ten subvariants. Of these, P-Thr-sv-1 and P-Thr-sv-3 have never been identified in Europe, while V-Val-sv-1 was newly discovered. Statistical analysis revealed significant differences in the distribution of EBNA1 P-Thr subvariants between the three groups of patients, with noticeable clustering of P-Thr-sv-5 in NPC isolates (p < 0.001). EBV EBNA1 showed no sequence specificity in primary infection. This research revealed a newly discovered EBNA1 subvariant. Importantly, EBNA1 P-Thr-sv-5 showed carcinoma-specific EBNA1 variability. Thus, identification of this subvariant should be considered as a viral screening marker for NPC or UCNT.
爱泼斯坦-巴尔病毒（EBV）已被确定为1类致癌物质，尤其是对于鼻咽癌（NPC）。EBV核抗原1（EBNA1）的序列多样性反映了区域限制性多态性，这可能与某些恶性肿瘤的发生有关。本研究的目的是评估在鼻咽癌、传染性单核细胞增多症以及器官移植患者分离株中循环的EBV EBNA1基因多态性，以确定EBNA1序列特异性是否可用作鼻咽癌的病毒生物标志物。本研究检测了40份鼻咽型未分化癌（UCNT）活检样本、31份单核细胞增多症综合征患者的血浆样本以及16份肾移植患者的血浆样本。通过巢式PCR扩增EBNA1基因。进一步的研究包括测序、系统发育和统计评估。87个序列被鉴定为四种EBNA1亚型之一，即P-Ala、P-Thr、V-Val和V-Ala，并进一步分类为十个亚变体。其中，P-Thr-sv-1和P-Thr-sv-3在欧洲从未被发现，而V-Val-sv-1是新发现的。统计分析显示，三组患者之间EBNA1 P-Thr亚变体的分布存在显著差异，鼻咽癌分离株中P-Thr-sv-5明显聚集（p < 0.001）。EBV EBNA1在初次感染时未显示序列特异性。本研究发现了一种新的EBNA1亚变体。重要的是，EBNA1 P-Thr-sv-5显示出癌特异性的EBNA1变异性。因此，该亚变体的鉴定应被视为鼻咽癌或UCNT的病毒筛查标志物。
