潛伏膜蛋白2A (LMP2A)，表達于大多數(shù)人類皰疹病毒(EBV)有關(guān)的惡性腫瘤,，已經(jīng)被證明是潛伏性感染及上皮細胞轉(zhuǎn)化的主要誘因,。
除此以外，它也可以作為基于CTL（cytotoxic T lymphocyte,，細胞毒性T淋巴細胞）治療EBV關(guān)聯(lián)的惡性腫瘤的靶點,。中國南部廣州有鼻咽癌(NPC)地方性發(fā)病區(qū)，在目前的研究中,，中山大學的邵春奎教授研究了該地區(qū)EBV相關(guān)的胃癌(EBVaGC)以及健康EBV攜帶者的LMP2A的序列變化,。
廣泛的序列變化發(fā)現(xiàn)于LMP2A基因，但是沒有與B95.8原型一致的序列,，并且在所有的隔離群里沒有發(fā)現(xiàn)一致突變,。在LMP2A氨基末端，免疫受體酪氨酸活化基序(ITAM)以及PY模體是嚴格保守的,，這表明,，它們對病毒感染起著重要的作用,。
研究發(fā)現(xiàn),，在LMP2A跨膜區(qū)域中的17個CTL抗原表位，有8個表位可以通過至少一個點突變受影響,。研究人員表示,，這可能暗示著在實施LMP2A定向免疫治療時應該考慮LMP2A多態(tài)性的作用。
殘胃癌(GRC)EBVaGC的LMP2A的多態(tài)性研究在世界上屬于首次研究，研究發(fā)現(xiàn)，殘胃癌 (GRC)EBVaGC中LMP2A的序列變化有些不同于常規(guī)胃癌,。
EBVaGC的LMP2A的序列變化類似于有咽喉疾病的健康的EBV攜帶者，表明這些變化起因于地理有關(guān)的多態(tài)性,，而不是因為EBVaGC關(guān)聯(lián)的突變,。
這是第一次詳細研究了EBVaGC中LMP2A的多態(tài)性,。相關(guān)文章發(fā)表在3月28日的PLoS One,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0034276
PMC:
PMID:
Sequence Variations of Latent Membrane Protein 2A in Epstein-Barr Virus-Associated Gastric Carcinomas from Guangzhou, Southern China
Jing Han, Jian-ning Chen, Zhi-gang Zhang, Hai-gang Li, Yun-gang Ding, Hong Du, Chun-kui Shao.
Latent membrane protein 2A (LMP2A), expressed in most Epstein-Barr virus (EBV)-associated malignancies, has been demonstrated to be responsible for the maintenance of latent infection and epithelial cell transformation.Besides, it could also act as the target for a CTL-based therapy for EBV-associated malignancies. In the present study, sequence variations of LMP2A in EBV-associated gastric carcinoma (EBVaGC) and healthy EBV carriers from Guangzhou, southern China, where nasopharyngeal carcinoma (NPC) is endemic, were investigated.Widespread sequence variations in the LMP2A gene were found, with no sequence identical to the B95.8 prototype. No consistent mutation was detected in all isolates. The immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs in the amino terminus of LMP2A were strictly conserved, suggesting their important roles in virus infection;while 8 of the 17 identified CTL epitopes in the transmembrane region of LMP2A were affected by at least one point mutation, which may implicate that the effect of LMP2A polymorphisms should be considered when LMP2A-targeted immunotherapy is conducted.The polymorphisms of LMP2A in EBVaGC in gastric remnant carcinoma (GRC) were for the first time investigated in the world. The LMP2A sequence variations in EBVaGC in GRC were somewhat different from those in EBVaGC in conventional gastric carcinoma.The sequence variations of LMP2A in EBVaGC were similar to those in throat washing of healthy EBV carriers, indicating that these variations are due to geographic-associated polymorphisms rather than EBVaGC-associated mutations.This, to our best knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC in Guangzhou, southern China, where NPC is endemic.
