据美国物理学家组织网报道,北卡罗莱纳大学科学家的一项最新发现显示,细胞感染人类疱疹病毒(EBV)后,会产生小泡或被称为外体的液囊,从而改变细胞中所含的蛋白质和RNA(核糖核酸)。这种变质的外体一旦进入健康细胞,就能转变细胞的良性生长方式,使之变成不可控的致癌生长。这一发现刊登于美国《国家科学院院刊》网络版。
EBV可能是世界上最成功的病毒,它无法被免疫系统彻底清除,几乎每个人终生都被它感染。它们不断进入唾液,在这里进行有效地传播。感染这种病毒很少致病,然而在几种主要的癌症中都发现了它的踪迹,包括淋巴瘤和鼻咽癌,它的蛋白质劫持了细胞生长调控机制,引发不可控的细胞生长,从而导致癌变。
研究认为一种名为潜伏膜蛋白质1的蛋白质是EBV的致癌基因。通过外体,它们被传递给未受感染的细胞。研究人员还指出,EBV也彻底改变了外体的内含物,在细胞之间传递能激活癌症的蛋白质,这是值得注意的地方。这些发现表明,通过这种方式,病毒感染细胞能广泛影响并潜在控制全身其他细胞,引发它们的不可测生长。
免疫系统不断地监视着外来病毒蛋白质,然而经外体携带的这些蛋白质可以不向免疫系统“报告”感染,并刺激癌细胞生长,由此容许了一种不可测的生长。该研究还显示,细胞能产生血管,这一被称为血管新生的过程很容易接受变质外体并引发潜在生长。
北卡罗莱纳大学莱恩伯格综合癌症研究中心微生物与免疫学教授南希·瑞玻-特拉玻说:“外体就像特洛伊木马,EBV通过木马甚至能控制那些还没有感染的细胞。但重要的是,外体的产生可能为我们提供了一种新的治疗标靶,封锁它们就能控制癌症蔓延。”
论文第一作者、瑞玻-特拉玻实验室博士后戴维·麦克表示,下一步研究是测定哪些蛋白质被选中进入外体,病毒如何控制了这些蛋白质,以及怎样才能遏制这一过程。(生物谷Bioon.com)
生物谷推荐英文摘要:
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.