瑞典卡羅林斯卡醫(yī)學(xué)院細(xì)胞和分子生物學(xué)系的研究者在最新一期的《美國科學(xué)院院刊》PNAS上發(fā)表文章,，解析EB病毒誘發(fā)癌癥的機(jī)制,。
EB病毒一種皰疹病毒即愛潑斯坦－巴爾二氏病毒（Epstein-Barr virus;EBV）的簡(jiǎn)稱，是1963年M.A.愛潑斯坦和Y.M.巴爾對(duì)非洲兒童罹患的伯基特氏淋巴瘤的細(xì)胞進(jìn)行體外組織培養(yǎng)時(shí)發(fā)現(xiàn)的,，故名,。此病毒是一種親淋巴細(xì)胞病毒，屬皰疹病毒科γ組,、能感染人及靈長類動(dòng)物的 B淋巴細(xì)胞,。EBV感染可能是鼻咽癌(尤其是未分化型鼻咽癌)的病因之一。研究證明,將鼻咽癌活體細(xì)胞進(jìn)行培養(yǎng),，可在癌細(xì)胞中發(fā)現(xiàn)EBV基因及EBV特異性抗原,。同時(shí)在鼻咽癌病人血清中發(fā)現(xiàn)多種 EBV抗體。鼻咽癌病人的血清和唾液中,，EBV特異性IgA抗體的滴度和陽性率均明顯高于正常人及其他腫瘤病人,。
據(jù)介紹，Maria Masucci及其同事研究了該病毒的一種蛋白質(zhì)在所有攜帶EBV的惡性腫瘤中表達(dá)的效應(yīng),，并搜尋了被稱為B細(xì)胞系的淋巴細(xì)胞的基因組不穩(wěn)定的跡象,，這是癌癥的一個(gè)標(biāo)志。這組作者找到了表達(dá)這種病毒蛋白質(zhì)的B細(xì)胞系,，并觀察到了這些細(xì)胞中的染色體異常,、DNA雙鏈破壞以及DNA損傷反應(yīng)激活的顯著增加。這種病毒此前已經(jīng)和Burkitt淋巴瘤,、霍奇金病,、鼻咽癌以及移植后淋巴組織增生性疾病聯(lián)系在了一起，但是它在這些疾病中扮演的角色尚未完全弄清,。這組科學(xué)家提出,，與EBV有關(guān)的核心抗原很可能增加了活性氧的制造，這會(huì)導(dǎo)致這種DNA損傷。這組科學(xué)家說,，這些發(fā)現(xiàn)可能有助于治療EBV相關(guān)疾病,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS Published online before print January 12, 2009, doi: 10.1073/pnas.0810619106
The Epstein–Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species
Bettina Gruhnea, Ramakrishna Sompallaea, Diego Marescottia,b, Siamak Akbari Kamranvara, Stefano Gastaldelloa,c and Maria G. Masuccia,1
The Epstein–Barr virus (EBV) nuclear antigen (EBNA)-1 is the only viral protein expressed in all EBV-carrying malignancies, but its contribution to oncogenesis has remained enigmatic. We show that EBNA-1 induces chromosomal aberrations, DNA double-strand breaks, and engagement of the DNA damage response (DDR). These signs of genomic instability are associated with the production of reactive oxygen species (ROS) and are reversed by antioxidants. The catalytic subunit of the leukocyte NADPH oxidase, NOX2/gp91phox, is transcriptionally activated in EBNA-1–expressing cells, whereas inactivation of the enzyme by chemical inhibitors or RNAi halts ROS production and DDR. These findings highlight a novel function of EBNA-1 and a possible mechanism by which expression of this viral protein could contribute to malignant transformation and tumor progression.
