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分析鼻咽癌和胃癌中 Epstein-Barr 病毒 EBNA-2 基因编码的氨基酸 148-487。

Sequence analysis of Epstein-Barr virus EBNA-2 gene coding amino acid 148-487 in nasopharyngeal and gastric carcinomas.

机构信息

Department of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, China.

出版信息

Virol J. 2012 Feb 21;9:49. doi: 10.1186/1743-422X-9-49.

DOI:10.1186/1743-422X-9-49
PMID:22348267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3312847/
Abstract

BACKGROUND

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) plays a key role in the B-cell growth transformation by initiating and maintaining the proliferation of infected B-cell upon EBV infection in vitro. Most studies about EBNA-2 have focused on its functions yet little is known for its intertypic polymorphisms.

RESULTS

Coding region for amino acid (aa) 148-487 of the EBNA-2 gene was sequenced in 25 EBV-associated gastric carcinomas (EBVaGCs), 56 nasopharyngeal carcinomas (NPCs) and 32 throat washings (TWs) from healthy donors in Northern China. Three variations (g48991t, c48998a, t49613a) were detected in all of the samples (113/113, 100%). EBNA-2 could be classified into four distinct subtypes: E2-A, E2-B, E2-C and E2-D based on the deletion status of three aa (294Q, 357K and 358G). Subtypes E2-A and E2-C were detected in 56/113 (49.6%), 38/113 (33.6%) samples, respectively. E2-A was observed more in EBVaGCs samples and subtype E2-D was only detected in the NPC samples. Variation analysis in EBNA-2 functional domains: the TAD residue (I438L) and the NLS residues (E476G, P484H and I486T) were only detected in NPC samples which located in the carboxyl terminus of EBNA-2 gene.

CONCLUSIONS

The subtypes E2-A and E2-C were the dominant genotypes of the EBNA-2 gene in Northern China. The subtype E2-D may be associated with the tumorigenesis of NPC. The NPC isolates were prone harbor to more mutations than the other two groups in the functional domains.

摘要

背景

EB 病毒(EBV)核抗原 2(EBNA-2)在体外 EBV 感染时通过启动和维持受感染 B 细胞的增殖,在 B 细胞生长转化中发挥关键作用。大多数关于 EBNA-2 的研究都集中在其功能上,但对其异型多态性知之甚少。

结果

对来自中国北方的 25 例 EBV 相关胃癌(EBVaGC)、56 例鼻咽癌(NPC)和 32 例咽拭子(TW)中的 EBNA-2 基因编码区的氨基酸(aa)148-487 进行了测序。在所有样本(113/113,100%)中均检测到三种变异(g48991t、c48998a、t49613a)。根据三个 aa(294Q、357K 和 358G)的缺失状态,EBNA-2 可分为四个不同的亚型:E2-A、E2-B、E2-C 和 E2-D。在 56/113(49.6%)、38/113(33.6%)样本中分别检测到 E2-A 和 E2-C 亚型。E2-A 更多见于 EBVaGC 样本,而 E2-D 亚型仅见于 NPC 样本。EBNA-2 功能域中的变异分析:TAD 残基(I438L)和 NLS 残基(E476G、P484H 和 I486T)仅在 NPC 样本中检测到,这些样本位于 EBNA-2 基因的羧基末端。

结论

在中国北方,EBNA-2 基因的 E2-A 和 E2-C 亚型是主要基因型。E2-D 亚型可能与 NPC 的肿瘤发生有关。与其他两组相比,NPC 分离株在功能域中更容易发生更多突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/0a150bbe5f7a/1743-422X-9-49-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/f65e030ad623/1743-422X-9-49-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/bfd97319e827/1743-422X-9-49-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/0a150bbe5f7a/1743-422X-9-49-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/f65e030ad623/1743-422X-9-49-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/bfd97319e827/1743-422X-9-49-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/295b/3312847/0a150bbe5f7a/1743-422X-9-49-3.jpg

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