应用微生物与肿瘤相关性研究成果为防治肿瘤服务

自从Rous肉瘤病毒被发现以来,许多学者们曾致力于研究肿瘤病毒病因,并已取得令人瞩目的成绩.虽然目前仅有人T淋巴细胞白血病病毒1型(HTLV-1)可以肯定为肿瘤的病因外,许多病毒如乙型肝炎病毒(HBV)与肝癌,人乳头瘤病毒与宫颈癌,EB病毒与Burkitt淋巴瘤、鼻咽癌,人类疱疹病毒8型(HHV-8)与Kaposi肉瘤间的高度相关性已不容置疑.     

肿瘤病毒及艾滋病病毒的分子生物学

肿瘤病毒——凡能在人和动物体内诱发肿瘤或转化体外培养细胞的病毒叫肿瘤病毒。人类的肿瘤病毒是在动物肿瘤病毒学基础上发展起来的。Ellerman和Bang首先(1908年)发现了鸡白血病,三年后Rous又发现了鸡肉瘤,30年代后相继发现兔、蛙、狗、鼠等种属的肿瘤病毒,特别是1951年Gross首先发现小鼠白血病病毒。近年来发现一些人类肿瘤和病毒的关系极为密切,如:EB病毒(Epstein-Barr Virus,1964年)和伯基特淋巴瘤、鼻咽癌;乙型肝炎病毒和原发性肝癌;人乳头状瘤一些病毒株和子宫颈癌等都有些证据。更重要是     

反向点杂交法快速诊断人乳头瘤病毒的基因型

人乳头瘤病毒(HPV)是迄今已被肯定的少数DNA肿瘤病毒之一,在女性下生殖道肿瘤中的检出率高达90％以上。HPV的DNA检测和分型对女性生殖道肿瘤的病因学和癌情预报具有重要意义。HPV异质性很大,用目前国内外传统的DNA诊断方法诊断未知样品的基     

病毒非编码RNA与肿瘤发生发展

超过12%的人类肿瘤与病毒密切相关,如Epstein-Barr virus(EBV)、high-risk human papillomaviruses(HPV)、hepatitis B virus(HBV)、hepatitis C virus(HCV)、Kaposi’s sarcoma herpesvirus(KSHV)等。传统观点认为病毒调控细胞恶性转化及肿瘤发生主要与病毒编码蛋白相关,但随着组学和测序技术发展,人们开始认识到病毒非编码RNA在肿瘤发生发展中的重要性。这些非编码RNA不翻译为蛋白质,仅在RNA水平参与对宿主细胞和病毒自身生命活动的多方面调控。现将针对长非编码RNA、短非编码RNA及microRNA在肿瘤中的调控进行综述。     

HBZ在人类T淋巴细胞白血病1型病毒HTLV-1致癌中的功能

人类T淋巴细胞白血病1型病毒(Human T-cell leukemia virus type 1,HTLV-1)是与人类疾病发生密切相关的逆转录病毒,HTLV-1的感染可引起成人T细胞白血病(Adult T-cell leukemia,ATL)。HBZ(HTLV-1bZIP factor)是由HTLV-1前病毒反义链编码的病毒蛋白。在HTVL-1所编码的病毒基因中,HBZ是唯一一个在所有ATL病人样品中持续、稳定表达的病毒基因。而且,HBZ在HTLV-1诱发肿瘤的过程中发挥着极其重要的作用。近十年来对HBZ结构及其功能的研究成为白血病研究领域的热点。因此,本文就HBZ在HTLV-1致癌机制方面的相关研究成果作一综述。     

肿瘤病毒诱导细胞异常增殖作用机制的研究进展

肿瘤是当前危害人类健康最严重的疾病,它以细胞增殖为主要病变特征.自从1911年Rous发现鸡肉瘤病毒可以使鸡发生白血病,人们就将病毒与肿瘤联系起来.本文就肿瘤病毒诱导细胞异常增殖作用机制方面分两部分进行阐述.     

揭开癌症发生机制之谜 从病毒致癌到细胞癌基因

<正>20世纪50年代,劳斯肉瘤病毒致癌现象逐渐被科学界接受,一方面促使科学界开始寻找更多的致癌病毒,另一方面也开始探索病毒致癌的分子机制,最终促使了细胞癌基因的发现,从而深化了对癌症发生的认识。病毒整合理论雷纳托·杜尔贝科(Renato Dulbecco)是一位意大利裔美国病毒学家,早期研究细菌病毒——噬菌体生     

人乳头瘤病毒的致瘤性及机制

高危型人乳头瘤病毒(HPV)可能引发多种癌症,公认的如宫颈癌和宫颈上皮内瘤变.近年来的研究表明,HPV还与头颈部鳞癌、食管癌及乳房癌等的发生密切相关.HPV引起头颈部鳞癌的机制在某种程度上与宫颈癌相似,但又有所不同.因此,阐明HPV的致癌机制对于HPV相关肿瘤的治疗具有重要意义.     

Nature:科学家提出头颈癌治疗新思路

<正>目前头颈部的鳞状细胞癌(HNSCC)是美国最为普遍的10种癌症之一,尽管其非常流行,但研究人员对其的发病及扩散的机制却是知之甚少,近日,一篇刊登在国际著名杂志Nature上的一篇研究论文中,来自耶鲁大学医学院的研究人员就为揭示头颈癌的发病机制提供了重要的信息。头颈癌是由一种名为人乳头瘤病毒(HPV)的病毒引发的,利用来自HPV阳性和阴性患者的肿瘤组织,研究人员就对其发生的突变或致癌基因进行了全面的分析和评估,研究者表示,癌基因在肿瘤的发生和转移过程中扮演着重要角色。     

CRISPR/Cas9基因编辑技术在致瘤病毒感染研究中的应用

成簇的规律间隔的短回文重复序列及其相关蛋白9〔clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9),CRISPR/Cas9〕基因编辑技术的发现源于真细菌和古细菌中CRISPR/Cas系统介导的适应性免疫机制研究。该技术利用特异性向导RNA识别靶点基因,引导核酸内切酶Cas9对其切割,并通过同源重组或非同源末端连接完成对目的DNA的编辑。某些病毒感染机体后,可将其基因组整合到宿主细胞基因组中或潜伏于组织中而无法被彻底清除,从而引起持续性感染。本文参考2013年以来CRISPR/Cas9基因组编辑技术的最新相关研究报道,重点综述其在人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)、人乳头瘤病毒(human papillomavirus,HPV )、乙型肝炎病毒(hepatitis B virus, HBV)、 Epstein-Barr病毒(Epstein-Barr virus,EBV)等致瘤病毒感染相关疾病研究中的应用,并概括其作用于这些病毒的有效靶点。     

New molecular mechanisms of virus-mediated carcinogenesis: oncogenic transformation of cells by retroviral structural protein Envelope

RNA tumor viruses as classified in Retroviruses have been isolated and identified to induce tumors in a variety of animals including chickens, mice, and rats, or even in human in the last 100 years, since the first one has been reported in 1908. The RNA tumor viruses have been historically classified into two groups, acute transforming RNA tumor viruses and nonacute RNA tumor viruses. Acute transforming RNA tumor viruses are basically replication-defective and rapidly induce tumors by expressing the viral oncogenes captured from cellular genome in host cells. The first oncogene derived from Rous sarcoma virus was the src non-receptor tyrosine kinase, which has been identified to play the significant roles for signal transduction. On the other hand, nonacute RNA tumor viruses, which consist of only gag, pro, pol, and env regions but do not carry oncogenes, are replication-competent and could activate the cellular proto-oncogenes by inserting the viral long terminal repeat close to the proto-oncogenes to induce tumors with a long incubation period, as is termed a promoter insertion. These molecular mechanisms have been thought to induce tumors. However, very recently several reports have described that the retroviral structural protein Envelope could directly induce tumors in vivo and transform cells in vitro. These are very unusual examples of native retroviral structural proteins with transformation potential. In this review we look back over the history of oncogenic retrovirus research and summarize recent progress for our understanding of the molecular mechanisms of oncogenic transformation by retrovirus Envelope proteins.     

Key characteristics of foods with an elevated risk for viral enteropathogen contamination

Viral enteropathogens are one of the leading causative agents of foodborne illnesses in both the United States and the European Union. While human noroviruses and hepatitis A virus cause the vast majority of outbreaks and illnesses, there are handful of human enteric viruses that contribute to sporadic outbreaks worldwide including astrovirus, sapovirus, rotavirus, enterovirus and Aichi virus. In addition, hepatitis E virus is increasingly being recognized as an emerging zoonotic threat within the food supply. This review aims to briefly describe the primary human enteric viruses of concern with respect to foodborne transmission. Next, we focus on the contamination and persistence of these viruses within three high-risk food commodities—leafy greens, soft red fruits and bivalve mollusks. As opposed to detailing the specific routes by which these foods can be contaminated with enteric viruses, we have chosen to focus on their persistence and specific interactions within the food itself. Therefore, the processes of attachment and internalization of the viruses in foods have been emphasized. Looking forward, the implications of these specific interactions of human enteric viruses with leafy greens, soft red fruits and bivalve mollusks are briefly considered within the context of future prevention and control strategies.     

Serological relationship of woodchuck hepatitis virus to human hepatitis B virus.

Two antigenic systems of the woodchuck hepatitis virus have been identified. The relationship between viral antigens of the woodchuck hepatitis virus and the human hepatitis B virus was determined by using immunoprecipitation, hemagglutination, and immune electron microscopy techniques. Antigens found on the cores of the two viruses were cross-reactive. Lack of cross-reactivity between the surface antigens of the two viruses in immunodiffusion experiments suggested that the major antigenic determinants of the viral surfaces are different; however, results of passive hemagglutination tests indicated that there are common minor determinants. Nucleic acid homology, as measured by liquid hybridization, was found to be 3 to 5% of the viral genomes. The results of this study provide further evidence that woodchuck hepatitis virus is the second member of a new class of viruses represented by human hepatitis B virus. Since virus-infected woodchucks may acquire chronic hepatitis and hepatocellular carcinoma, these antigens and their respective antibodies will be useful markers for following the course of virus infection in investigations of the oncogenic potential of this class of viruses. The nucleocapsid antigen described may be a class-specific antigen of these viruses and, thus, may be useful in discovering new members of the group.     

Virus proteins similar to human proteins as possible disturbance on human pathways

Cancer is not rare anywhere in the world now, and the global burden of cancer continues to increase largely every year. Previous research on infections and cancers reported that, about 17.8 % of the cancers worldwide, which are over 1.9 million cases of cancer, are related to viral infections. At least six oncoviruses, cancer-causing viruses, have been known so far, which include hepatitis B virus, hepatitis C virus, Epstein–Barr virus (EBV or HHV-4), human papillomavirus, human T lymphotropic virus type 1, Kaposi’s sarcoma-associated herpesvirus (KSHV or HHV-8), but the pathogenic mechanism is far from being completely understood. In this study, assuming that finding human proteins significantly similar to viral oncoproteins leads to a categorization of the cancer-related pathways that are currently not clearly known, we analyzed different types of virus-caused cancers based on their similarity in order to clarify the unknown cancer mechanisms. As a result, we obtained several potential tumor pathways that may be significant and essential in oncogenic cancer process, which will be helpful for further study on cancer mechanisms and the development of new drug targets.

Electronic supplementary material

The online version of this article (doi:10.1007/s11693-014-9141-y) contains supplementary material, which is available to authorized users.     

Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.     

Virus-associated human tumors: cervical carcinomas and papilloma viruses

The latest experimental data on the role of viruses in the origin of human tumors are discussed. This group of viruses consists of T-cell leukemia virus type 1 (HTLV 1), herpes viruses (HHV 8 and Epstein-Barr virus), hepatitis B virus, and human papilloma viruses. The most typical feature of this group of viruses is a very long latent period from the initial infection to the development of the disease that varies between 10 and 40 years. The mechanism of malignant cell conversion is specific for each viral type but is mainly associated with a disruption of functions of cellular genes participating in the control of cell division and proliferation. It can be a direct inactivation of tumor suppressor genes by their interaction with viral gene products (papilloma viruses), or a trans-activation of cellular genes modulating cell proliferation by viral gene products (hepatitis B virus and HTLV 1). Viruses play an initiative role and additional genetic changes in the genome of infected cells are necessary for complete expression of the oncogenic potential of the viral genes. Only these cells will give rise to a monoclonal cell population with uncontrolled proliferation. New approaches for the creation of vaccines against cancers associated with hepatitis B virus and papilloma viruses (hepatocellular carcinomas and cervical tumors, respectively) are in progress. These vaccines have been found to be effective in prevention of the disease in the experimental models and are now beginning to be used for human vaccination.     

Viral infections and cancer: epidemiological aspects.

Viral infections represent one of the areas in which cancer research has made the greatest advances in the last 20 years. In 1981, only two viruses were known to cause human cancer, i.e., the Epstein-Barr virus (EBV) and the hepatitis B virus (HBV). By 1995, it was estimated that approximately 15% of all cancers occurring world-wide were attributable to viral infections, and the oncogenic role of seven viruses [i.e., EBV, HBV, hepatitis C virus (HCV), human papillomavirus (HPV), human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), and human T cell leukemia virus type I (HTLV-I)] has been well-established. In this paper, the epidemiological evidence concerning some of the major aspects of the association between viruses and cancer are summarised.