EB病毒(Epstein-Barr Virus,EBV)属于γ疱疹病毒科,是第一个被发现与人类肿瘤相关的DNA病毒。EB病毒通过激活Toll样受体(Toll like receptors,TLRs)信号通路,诱导I型干扰素的大量释放和功能性的自噬机制,从而引起机体的免疫应答。然而,相对于其他疱疹病毒,EB病毒已进化出更为精细且错综复杂的机制来破坏和逃逸宿主的免疫系统,如限制自身蛋白表达、活化宿主的泛素-蛋白酶体系统、干扰或逆转自噬与泛素化修饰等。这些机制会引发EB病毒在宿主体内的持续性感染,导致宿主免疫功能失调,引发EB病毒相关疾病(如鼻咽癌、传染性单核细胞增多症等)。因此,研究EB病毒特异性的免疫调控机制不仅对深入理解EB病毒的潜伏性感染和致癌性至关重要,而且还将为EB病毒诱发的相关疾病的免疫预防与治疗鉴定出新的潜在靶点。此文主要阐述了EB病毒调控宿主免疫应答和逃逸先天免疫应答的分子机制。 相似文献
Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans. To ensure its survival and maintain its B cell transformation function, EBV has developed powerful strategies to evade host immune responses. Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis. In this review, we summarize current progress on how EBV utilizes miRNAs for immune evasion. EBV encodes miRNAs targeting both viral and host genes involved in the immune response. The miRNAs are found in two gene clusters, and recent studies have demonstrated that lack of these clusters increases the CD4+ and CD8+ T cell response of infected cells. These reports strongly indicate that EBV miRNAs are critical for immune evasion. In addition, EBV is able to dysregulate the expression of a variety of host miRNAs, which influence multiple immune-related molecules and signaling pathways. The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion, viral proteins, immune cells, chemokines, pro-inflammatory cytokines, and pro-apoptosis molecules are involved. Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.
The Epstein-Barr virus (EBV) is a human herpesvirus that is usually carried lifelong as an asymptomatic infection. EBV is the causative agent of infectious mononucleosis and has been linked to the development of several malignant tumours, including B-cell neoplasms such as Burkitt's lymphoma and Hodgkin's disease, certain forms of T-cell lymphoma, and some epithelial tumours, such as undifferentiated nasopharyngeal carcinoma and a proportion of gastric cancers. All these tumours are characterised by the presence of multiple extrachromosomal copies of the circular viral genome in the tumour cells and the expression of EBV-encoded latent genes, which appear to contribute to the malignant phenotype. An increasing understanding of the function of EBV latent genes and of the nature of the immune response to the virus is providing exciting new possibilities for the treatment of EBV-associated malignancies. For example, adoptive transfer of virus-specific cytotoxic T lymphocytes has already been of value in the treatment of EBV-positive B-cell lymphomas arising in post-transplant patients, and this approach is currently being investigated in other EBV-associated tumours. In addition, gene therapy offers the opportunity to deliver agents that might directly interfere with the function of specific EBV genes. This review summarises the role of EBV in malignancy. In particular, it focuses on the latent proteins as a basis for understanding how EBV might contribute to the process of transformation. Strategies to target EBV in tumours, potentially providing alternative therapeutic approaches, are also discussed. 相似文献
Epstein-Barr virus (EBV) is associated with about 6 to 16% of gastric carcinoma cases worldwide. Expression of the EBV microRNAs (miRNAs) was observed in B cells and nasopharyngeal carcinoma cells infected with EBV. However, it is not clear if the EBV miRNAs are expressed in EBV-associated gastric carcinomas (EBVaGCs). We found that BART miRNAs but not BHRF1 miRNAs were expressed in EBV-infected gastric carcinoma cell lines and the tumor tissues from patients as well as the animal model. The expression of viral miRNAs in EBVaGCs suggests that these EBV miRNAs may play important roles in the tumorigenesis of EBVaGCs. 相似文献
Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the
exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid
and epithelial malignancies, such as Hodgkin’s lymphoma, NK-T cell lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma.
EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins
are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins. Studies
have shown that EBV displays distinct patterns of viral latent gene expression in these lymphoid and epithelial tumors. The
constant expression of latent membrane protein 2A (LMP2A) at the RNA level in both primary and metastatic tumors suggests
that this protein might be a driving factor in the tumorigenesis of EBV-associated malignancies. LMP2A may cooperate with
the aberrant host genome, and thereby contribute to malignant transformation by intervening in signaling pathways at multiple
points, especially in the cell cycle and apoptotic pathway. This review summarizes the role of EBV-encoded LMP2A in EBV-associated
viral latency and cancers. We will focus our discussions on the molecular interactions of each of the conserved motifs in
LMP2A, and their involvement in various signaling pathways, namely the B-cell receptor blockade mechanism, the ubiquitin-mediated
(Notch and Wnt) pathways, and the MAPK, PI3-K/Akt, NK-κB and STAT pathways, which can provide us with important insights into
the roles of LMP2A in the EBV-associated latency state and various malignancies. 相似文献
The Epstein-Barr virus (EBV) is ubiquitous worldwide, with greater than 80% of people over the age of 30 having been infected. Once EBV infection has occurred, it remains for the lifetime of the individual, making EBV one of the most persistant viruses that infect humans. EBV is strongly associated with the development of several cancers, in particular with Burkitt's lymphoma, Hodgkin's disease, and lymphoproliferative disorders which complicate immune suppression conditions. These EBV-associated neoplasms are characterized by peculiar geographic distributions and distinctive epidemiologic features. In this review, the main epidemiological aspects of the relationship between EBV infection and cancer are outlined, and recent advances in the mechanisms underlying EBV-induced growth transformation are summarized. 相似文献
Epstein-Barr virus (EBV) is the DNA tumor virus, which is known to be relevant to various cancers. EBV maintains latent infection in cancer cells, and there are three types of latent infection (type I-III) according to the patterns of viral latent genes expression. EBV has the ability to transform B cells into immortalized lymphoblastoid cell lines (LCL) showing type III latency, in which all latent genes are expressed. The mechanism of B-cell transformation has provided a model of EBV-associated lymphomas in immunosuppressed individuals. In type I and II latency, the limited numbers of latent genes are expressed. Previous studies have demonstrated the oncogenic functions of latent EBV genes including nuclear antigen EBNA1, membrane protein LMP1 and LMP2A. In addition, we have demonstrated that EBV-encoded small RNA EBERs play a significant role in oncogenesis. Here we summarize recent progresses in the studies on molecular mechanisms of EBV-mediated oncogenesis. 相似文献
Epstein-Barr Virus (EBV) is an ubiquitous human herpesvirus which can lead to infectious mononucleosis and different cancers. In immunocompromised individuals, this virus is a major cause for morbidity and mortality. Transplant patients who did not encounter EBV prior to immunosuppression frequently develop EBV-associated malignancies, but a prophylactic EBV vaccination might reduce this risk considerably. Virus-like particles (VLPs) mimic the structure of the parental virus but lack the viral genome. Therefore, VLPs are considered safe and efficient vaccine candidates. We engineered a dedicated producer cell line for EBV-derived VLPs. This cell line contains a genetically modified EBV genome which is devoid of all potential viral oncogenes but provides viral proteins essential for the assembly and release of VLPs via the endosomal sorting complex required for transport (ESCRT). Human B cells readily take up EBV-based VLPs and present viral epitopes in association with HLA molecules to T cells. Consequently, EBV-based VLPs are highly immunogenic and elicit humoral and strong CD8+ and CD4+ T cell responses in vitro and in a preclinical murine model in vivo. Our findings suggest that VLP formulations might be attractive candidates to develop a safe and effective polyvalent vaccine against EBV. 相似文献
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