EBV感染相关性疾病的研究现状

Epstein-Barr病毒(Epstein-Barr Virus,EBV),简称EBV,属于疱疹病毒γ亚科嗜B淋巴细胞组群中的线性双链DNA病毒,又称人类疱疹病毒4型(Human Herpesvirus 4,HHV),是人类发现的第一个致癌病毒。EBV是传染性单核细胞增多症的原因,也与自身免疫病和多种肿瘤相关,如:Burkitt淋巴瘤、鼻咽癌、毛细胞白血病,和原发性中枢神经系统淋巴瘤。EBV能够潜伏感染B淋巴细胞,刺激B细胞增生转化,从而引起全身各个部位的疾病。现将EBV相关疾病进行详细阐述。     

EB病毒疫苗研究进展北大核心

EB病毒（EBV）是一种感染人的γ-疱疹病毒,与人类很多疾病有关,如单核细胞增多症、鼻咽癌、霍奇金淋巴瘤、伯基特淋巴瘤、移植后淋巴细胞增生症等。EBV相关疫苗作为预防EBV感染和治疗EBV相关肿瘤的手段一直以来是疫苗领域研究的热点。预防性疫苗是以病毒的包膜糖蛋白为靶蛋白,刺激机体产生中和抗体阻止病毒感染;治疗性疫苗主要用于治疗EBV潜伏感染相关的恶性肿瘤,是以肿瘤细胞中表达的EBV蛋白为靶位,刺激机体产生细胞免疫反应,增强毒性T淋巴细胞对肿瘤细胞的杀伤作用。本文从预防性疫苗和治疗性疫苗两方面对EBV疫苗的研究进展进行阐述。     

EB病毒疫苗研究进展

EB病毒(EBV)是一种感染人的γ-疱疹病毒,与人类很多疾病有关,如单核细胞增多症、鼻咽癌、霍奇金淋巴瘤、伯基特淋巴瘤、移植后淋巴细胞增生症等。EBV相关疫苗作为预防EBV感染和治疗EBV相关肿瘤的手段一直以来是疫苗领域研究的热点。预防性疫苗是以病毒的包膜糖蛋白为靶蛋白,刺激机体产生中和抗体阻止病毒感染;治疗性疫苗主要用于治疗EBV潜伏感染相关的恶性肿瘤,是以肿瘤细胞中表达的EBV蛋白为靶位,刺激机体产生细胞免疫反应,增强毒性T淋巴细胞对肿瘤细胞的杀伤作用。本文从预防性疫苗和治疗性疫苗两方面对EBV疫苗的研究进展进行阐述。     

儿童EB病毒感染与系统性红斑狼疮相关性的研究进展

正EB病毒(EBV)于1964年被发现,是人类疱疹病4型,长度为172 kb的双链DNA,具有衣壳和包膜~([1])。EB病毒感染在儿科常见,包括增殖型感染(或称活动性感染)和潜伏感染两种状态,初次感染后病毒可以长期在人上呼吸道上皮细胞或淋巴组织中潜伏~([2])。在中国,8岁以上人群90%以上血清学阳     

EB病毒在HIV感染早期的作用

EB病毒是一种广为传播的人类疱疾病毒,是急性单核细胞增多症的致病因子,并与多种淋巴增生性疾病,如鼻咽癌等有关。它广泛地分布于世界各地不同人群,于幼儿期就可感染,感染后常以潜伏的形式存在。有证据显示EB病毒在AIDS患者间或在有发展为AIDS的过程中起着某种作用,例如EBV抗体滴度增高,口咽部EBV分泌增多,血循环中感染了EBV的B细胞增多,以及可以从AIDS患者血中分离到EBV等。EBV在机体有免疫力时是处于潜伏状态的,但当HIV感染导     

KSHV潜伏和裂解感染机制的研究进展

卡波氏肉瘤相关疱疹病毒（KSHV）是卡波氏肉瘤（kapois’sarcoma,KS）的病原,并与PEL、MCD等多种淋巴增殖紊乱性疾病相关。其生命周期可分为潜伏感染和裂解感染两个阶段。在潜伏感染阶段,KSHV的病毒基因表达受到严格调控,只有少数病毒潜伏相关基因的持续表达,潜伏感染对病毒长期持续感染复制是必不可少的。在裂解复制阶段,病毒基因绝大部分复制表达,并包装产生新的感染性病毒颗粒。现就KSHV病毒潜伏感染和裂解感染机制的研究进展作一综述。     

应用PCR技术检测女性泌尿生殖道EB病毒感染分析

宫颈病毒(EBV)是一种人类疱疹病毒,多经唾液传播,少数可经输血途径传播,EBV常感染幼儿,且终生存在,如原发感染延迟到青壮年时发生,则多发生单核细胞增多症。EBV通常先感染口腔粘膜上皮细胞,然后进入血液感染B淋巴细胞,研究证明其与鼻咽癌及Burkitt淋巴细瘤的发生有密切关系。由于EBV的转化能力及其致癌性,人们非常重视对它的研究,目前不但完全清楚EBV的全部DNA序列,而且对其基因水平的表达调控也作了较深入的研究。近年来国外学者研究发现,EBV除感染粘膜上皮细胞,还可通过性行为传播。我     

EB病毒转化的抗体分泌B细胞系的研究及进展

自从1977年 Rosen 等首先用实验证明EB 病毒(Epstein-Barr Virus,EBV)可以在体外直接感染纯化的人外周血淋巴细胞,刺激多克隆免疫球蛋白的分泌以来,EBV 这一特性已经得到了广泛的研究和应用。EBV 感染 B 淋巴细胞后,可以使其无限期传代(Immortalization),成为能分泌免疫球蛋白的细胞系。这种 B 细胞系为免     

EB病毒感染与淋巴瘤发病机制的研究进展

[摘要]?EB病毒（Epstein-Barr virus, EBV）属于人类疱疹病毒γ亚科，是双链DNA病毒，与多种疾病的发生发展相关，是最早被发现与人类肿瘤相关的病毒。研究发现，霍奇金淋巴瘤、部分B细胞淋巴瘤、NK/T细胞淋巴瘤等在内的多种淋巴瘤的发生与EBV感染有关。本文就EBV与淋巴瘤的关系、致病机制、相关临床研究进展进行综述。     

猫免疫缺陷病毒和猫艾滋病

猫免疫缺陷病毒(FIV)是慢病毒亚科的最新成员,具有复杂的基因组结构.病毒在体内感染T淋巴细胞、巨噬细胞和脑星形胶质细胞.感染猫潜伏几年后发病,表现一组免疫缺陷样复合病征(Th淋巴细胞选择性消耗和CD4+/CD8+淋巴细胞比率下降)和机会性感染.如果有协同因子如猫白血病病毒(FeLV)混合感染,则症状严重,潜伏时间缩短.FIV感染呈地方性流行,世界性分布,主要由于游走猫之间的撕咬经唾液和血液水平传播.在所有慢病毒宿主中,猫可作为人艾滋病的分子致病机理、药物的筛选和治疗,以及疫苗等方面研究的动物模型.     

Epstein-Barr病毒EBER基因及其生物学特性研究进展

Epstein-Barr病毒（EB病毒）与传染性单核细胞增多症、继发性噬血细胞性淋巴组织细胞增生症和鼻咽癌等相关,是重要的肿瘤相关病毒.EBERs是EB病毒潜伏感染的细胞内数量最多的病毒转录产物,可能在潜伏感染及细胞转化中发挥重要的作用.此文综述了EBER基因变异及EBERs的生物学特性.     

Rabbits immunized with Epstein-Barr virus gH/gL or gB recombinant proteins elicit higher serum virus neutralizing activity than gp350

Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been strongly implicated in the etiology of multiple epithelial and lymphoid cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder. There is currently no licensed prophylactic vaccine for EBV. Most efforts to develop prophylactic vaccines have focused on EBV gp350, which binds to CD21/CD35 to gain entry into B cells, and is a major target of serum neutralizing antibody in EBV seropositive humans. However, a recombinant monomeric gp350 protein failed to prevent EBV infection in a phase II clinical trial. Thus, alternative or additional target antigens may be necessary for a successful prophylactic vaccine. EBV gH/gL and gB proteins coordinately mediate EBV fusion and entry into B cells and epithelial cells, strongly suggesting that vaccination with these proteins might elicit antibodies that will prevent EBV infection. We produced recombinant trimeric and monomeric EBV gH/gL heterodimeric proteins and a trimeric EBV gB protein, in addition to tetrameric and monomeric gp350^1–470 proteins, in Chinese hamster ovary cells. We demonstrated that vaccination of rabbits with trimeric and monomeric gH/gL, trimeric gB, and tetrameric gp350^1–470 induced serum EBV-neutralizing titers, using cultured human B cells, that were >100-fold, 20-fold, 18-fold, and 4-fold higher, respectively, than monomeric gp350^1–470. These data strongly suggest a role for testing EBV gH/gL and EBV gB in a future prophylactic vaccine to prevent EBV infection of B cells, as well as epithelial cells.     

Epstein-Barr virus genome positive lymphoepithelioma-like carcinoma of the stomach]

EBV is associated with a high number of tumours and non-tumourous conditions. The rare lymphoepithelioma like carcinoma of the stomach,--just as similar tumours of foregut origin (thymus, lung, salivary gland)--are frequently EBV genom positive with the expression of only a few genes (EBV nuclear antigen 1, EBV encoded ribonucleoproteins/EBER/, latency I). On the basis of the clinicopathological analysis of two cases and literature data the authors point out the male predominance and the relatively favourable prognosis of the patients, furthermore the frequent cardial-subcardial localization of these tumours. Since the frequent non-lymphoepithelioma like stomach tumours,--adenocarcinomas,--show EBV genom positivity in about 1% of the cases, it is concluded that the characteristic lymphoepithelioma like histological pattern is not a sine qua non condition of EBV genom positivity. It may also be assumed, that the CD8 and TIA 1 cytotoxic lymphocytes are not virus but tumour cell specific, however not efficient, perhaps not activated. The low level of apoptotic tumour cells supports this assumption. In one of the cases a double tumour, a genom positive lymphoepithelioma like carcinoma and a genom negative adenocarcinoma, adjacent to each other was seen which speaks in favour of common carcinogenetic factors and shows that microscopic neighbourhood is not a necessary condition in viral association. The origin of the possible oncogenic effect of EBV in the absence of the transforming gene products latent membrane protein 1 and EBNA 2 in genom positive stomach carcinomas is uncertain. The significance of the presence in both cases of CD 5+ tumour cells is not clear, the study of further cases is indicated.     

Assessment of the relationship of chronic opisthorchiasis to Epstein–Barr virus infection as well as some cytogenetical and immunological parameters in two comparable Siberian regions

Previous studies have shown an increase in the frequency of chromosomal abnormalities in the peripheral blood lymphocytes from opisthorchiasis patients. Some evidence suggests that there is an association between chronic opisthorchiasis and certain herpes viruses. To study the relationship of opisthorchiasis to the reactivation of Epstein–Barr virus (EBV) infection as well as the influence of opisthorchis infection on some cytogenetical and immunological parameters, we used the indirect immunofluorescence for measuring some virus specific antibodies, the cytokinesis-block lymphocyte micronucleus assay, and the quantitative immunodiffusion method for measuring immunoglobulin concentrations in serum. A total of 1,580 people were monitored in two comparable Siberian regions: in the Ob River region which is endemically related to opisthorchiasis caused by Opisthorchis felineus and in the nonendemic control Yenisey River region. There was no significant difference in each of the tested parameters between two uninfected controls from the endemic Ob and nonendemic Yenisey regions. We have found significant difference (p < 0.01) in the frequency of micronucleated cytokinesis-block lymphocytes and the antibody levels against certain EBV antigens between the examined inhabitants of the opisthorchis-infected Ob and uninfected Yenisey regions. Furthermore, there were a good correlation (r = +0.72) between the increase in titres of antibody to the EBV capsid antigen and the high frequency of micronucleated lymphocytes in the opisthorchis-infected Ob population. Also, levels of both IgG and IgM were increased in opisthorchiasis patients. This study confirms an association between chronic opisthrochiasis and reactivation of EBV which may be implicated in the development of cancer in opisthorchiasis patients.     

A novel high throughput assay to quantify Epstein-Barr virus neutralizing antibody activity against B-cell and epithelial cell infections for vaccine and therapeutic developments

Epstein-Barr Virus (EBV) is the causative agent of infectious mononucleosis and has been associated with a variety of malignancies. In vivo, EBV infects B cells and epithelial cells. However, the current EBV neutralization assays, especially those against B cell infection, are low throughput, laborious and lack of sensitivity. In this study, we optimized the EBV-GFP based micro-neutralization assay by selecting the most susceptible cell substrates, Akata 4E3 for B cell and HEK293T for epithelial cell. The newly developed procedure is high throughput. The cell type specific neutralization was confirmed using monoclonal antibodies specific to gp350 and gH/gL/gp42. A panel of human sera was also tested. Natural human EBV seropositive sera could neutralize EBV in both B cell and epithelial cell assays efficiently with a majority of human sera generating near 100% EBV neutralization. The EBV neutralizing antibody titers were highly correlated with antibodies specific to gp350, gH, EBV total proteins, and to a less degree with antibodies against gp42. Collectively, we demonstrated this improved neutralization assay is suitable to evaluating the humoral responses elicited by EBV vaccine candidates in preclinical animal models or in large-scale human trials.     

In situ hybridization in undifferentiated nasopharynx carcinoma in Tunisia. Report of 3 cases

The undifferentiated carcinoma of nasopharyngeal type (UCNT) is highly prevalent in South East Asia countries and has intermediate incidence in Tunisia, where Epstein-Barr virus constitutes one of the key factors of oncogenesis. Our preliminary results, in 3 patients with UCNT, show an elevated rate of EBV antibodies and a latent infection (type II) (expression of LMP and absence of ZEBRA by immunohistochemical reaction) and a positive staining with EBERs probe by in situ hybridation (ISH) in all cases. These results confirm a close association between EBV and tunisian UCNT. Moreover, the use of HIS technique for detection of EBERs constitutes an additional and formal argument of this association.     

Epstein-Barr病毒基因表达在儿童SLE中作用的研究

摘要:目的　通过研究EB病毒（EBV）基因在儿童系统性红斑狼疮（SLE）中的表达,探讨EBV在儿童SLE发病中的作用。方法　（1）分离20例SLE患儿和12例健康对照外周血单核细胞（PBMCs）。（2）用ELISA检测EBV-IgG/IgM阳性的SLE患儿,取其分泌EBV病毒的细胞上清液与提取的PBMCs共同培养12 d,提取培养后的PBMCs的RNA,用逆转录实时定量PCR（RT-PCR）的方法检测EBV基因的表达。结果　SLE患儿组伏期基因LMP1、LMP2、EBNA-1和裂解期基因BCRF1、BLLF1的表达均显著高于健康对照组,差异有统计学意义（分别为1.011±0.145比0.383±0.180,t＝10.680,P＜0.05;1.001±0.096比0.208±0.086,t＝25.109,P＜0.05;1.012±0.168比0.188±0.157,t＝14.591,P＜0.05;1.015±0.171比0.344±0.169,t＝10.680,P＜0.05;1.038±0.271比0.117±0.085,t＝10.680,P＜0.05）。结论　儿童SLE患者中存在EBV基因的异常表达,EBV基因可能参与了SLE的发病过程。     

Infections due to the human herpesviruses in southern India: a seroepidemiological survey

We studied the prevalence of IgG and IgM antibodies to the human herpesviruses in a hospital-based population of 181 individuals aged 0 to 25 years, who were resident in Vellore, south India or surrounding rural areas. Antibodies to the Epstein-Barr virus (EBV) viral capsid antigen were determined by indirect immunofluorescence, while antibodies to the remaining herpesviruses were determined by enzyme-linked immunosorbent assay. The age-specific prevalence rates of IgG antibodies to EBV and cytomegalovirus (CMV) rose rapidly after birth to reach a value of over 90% by the fourth year of life. High age-specific IgM prevalence rates and geometric mean titres (GMT) of IgG antibody in children 6 months to 2 years of age, and the early median age of virus infection (1.4 years for EBV and less than 1 year for CMV) indicate that primary infection with these viruses occurs early in life. In contrast, age-specific prevalence rates of IgG antibodies to varicella-zoster virus (VZV) and herpes simplex virus (HSV) rose gradually after birth to attain maximal values of only 72% (VZV) and 83% (HSV) in the 15-25 year age group, and the median ages of infection were delayed (12.25 years for VZV and 8.2 years for HSV). The age-specific IgG prevalence rates of VZV and HSV, and of EBV and HSV showed statistically significant positive correlations, suggesting that common epidemiological factors may underlie the pattern of infections due to these groups of viruses.(ABSTRACT TRUNCATED AT 250 WORDS)     

EBV感染患儿临床特征及血清免疫因子水平

目的分析124例巴尔病毒(EBV)感染患儿的临床特征和血清免疫因子水平。方法选择2016年12月-2019年12月于海南医学院第一附属医院确诊的124例EBV感染患儿为研究组,根据临床表现分为传染性单核细胞增多症(IM)组43例和单纯性EBV组81例,选择同期健康体检儿童62名为对照组。记录所有患儿入组时的年龄、性别、临床症状;荧光定量PCR反应检测外周血淋巴细胞中EBV DNA载量;检测血清白细胞介素-6(IL-6)、IL-2和肿瘤坏死因子-α(TNF-α)水平,流式细胞仪分析外周血T淋巴细胞水平;Pearson相关性分析外周血T淋巴细胞亚群与EBV DNA载量之间的相关性。结果 IM组患儿的年龄为(5.13±1.56)岁,大于单纯性EBV组(P<0.05),出现发热、咽峡炎、淋巴结肿大、脾肿大、肝肿大、眼睑水肿、鼻塞、打鼾的比例为88.37%、93.02%、93.02%、48.84%、60.47%、32.56%、55.81%和46.51%,高于单纯性EBV组(P<0.05);IM组患儿的血CD3+T、CD8+T细胞、IL-6、TNF-α为分别为(73.25±7.16)%、(40.19±4.21)%、(33.68±5.71)ng/L、(72.52±11.26)ng/L高于对照组,而CD4+T、CD4+/CD8+T细胞、IL-2分别为(34.86±3.75)%、(0.89±0.15)、(10.43±3.38)ng/L则均低于对照组(P<0.05);外周血CD3+T和CD8+T细胞水平均与病毒载量呈正相关(r=0.314,0.447,P<0.05),CD4+T和CD4+/CD8+T细胞水平与病毒载量呈负相关(r=-0.425,-0.376,P<0.05)。结论 EBV感染患儿的临床症状和细胞免疫功能与病毒载量有关,有望应用于临床评估EBV感染的病情发展。