據(jù)美國物理學(xué)家組織網(wǎng)報道,，北卡羅萊納大學(xué)科學(xué)家的一項最新發(fā)現(xiàn)顯示,，細(xì)胞感染人類皰疹病毒(EBV)后,，會產(chǎn)生小泡或被稱為外體的液囊,，從而改變細(xì)胞中所含的蛋白質(zhì)和RNA(核糖核酸),。這種變質(zhì)的外體一旦進(jìn)入健康細(xì)胞,，就能轉(zhuǎn)變細(xì)胞的良性生長方式,，使之變成不可控的致癌生長。這一發(fā)現(xiàn)刊登于美國《國家科學(xué)院院刊》網(wǎng)絡(luò)版,。
EBV可能是世界上最成功的病毒,，它無法被免疫系統(tǒng)徹底清除，幾乎每個人終生都被它感染,。它們不斷進(jìn)入唾液,，在這里進(jìn)行有效地傳播。感染這種病毒很少致病,，然而在幾種主要的癌癥中都發(fā)現(xiàn)了它的蹤跡,，包括淋巴瘤和鼻咽癌，它的蛋白質(zhì)劫持了細(xì)胞生長調(diào)控機(jī)制,，引發(fā)不可控的細(xì)胞生長,，從而導(dǎo)致癌變。
研究認(rèn)為一種名為潛伏膜蛋白質(zhì)1的蛋白質(zhì)是EBV的致癌基因,。通過外體,，它們被傳遞給未受感染的細(xì)胞。研究人員還指出,，EBV也徹底改變了外體的內(nèi)含物,，在細(xì)胞之間傳遞能激活癌癥的蛋白質(zhì),，這是值得注意的地方。這些發(fā)現(xiàn)表明,，通過這種方式,，病毒感染細(xì)胞能廣泛影響并潛在控制全身其他細(xì)胞，引發(fā)它們的不可測生長,。
免疫系統(tǒng)不斷地監(jiān)視著外來病毒蛋白質(zhì),，然而經(jīng)外體攜帶的這些蛋白質(zhì)可以不向免疫系統(tǒng)“報告”感染，并刺激癌細(xì)胞生長,，由此容許了一種不可測的生長,。該研究還顯示，細(xì)胞能產(chǎn)生血管,，這一被稱為血管新生的過程很容易接受變質(zhì)外體并引發(fā)潛在生長,。
北卡羅萊納大學(xué)萊恩伯格綜合癌癥研究中心微生物與免疫學(xué)教授南希·瑞玻-特拉玻說：“外體就像特洛伊木馬，EBV通過木馬甚至能控制那些還沒有感染的細(xì)胞,。但重要的是,，外體的產(chǎn)生可能為我們提供了一種新的治療標(biāo)靶，封鎖它們就能控制癌癥蔓延,。”
論文第一作者,、瑞玻-特拉玻實驗室博士后戴維·麥克表示，下一步研究是測定哪些蛋白質(zhì)被選中進(jìn)入外體,，病毒如何控制了這些蛋白質(zhì),，以及怎樣才能遏制這一過程。（生物谷Bioon.com）
生物谷推薦英文摘要：
PNAS doi: 10.1073/pnas.1014194107
Human tumor virus utilizes exosomes for intercellular communication
David G. Meckes, Jr.a, Kathy H. Y. Shaira, Aron R. Marquitza, Che-Pei Kungb, Rachel H. Edwardsa, and Nancy Raab-Trauba,b,1
aThe Lineberger Comprehensive Cancer Center, and
bDepartment of Microbiology–Immunology, University of North Carolina, Chapel Hill, NC 27599
The Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs.
