体外抑制EB病毒药物的应用研究

EB病毒容易感染人,与人类许多疾病高度相关,严重威胁人类健康。目前尚无有效的预防EB病毒感染的措施且针对EB病毒的药物比较局限,故而对EB病毒感染进行治疗显得十分重要。近年来研究发现,许多药物在体外可对EB病毒有很好的抑制效果。仅就体外抑制EB病毒的药物,如核苷类似药、硼替佐米、寡脱氧核苷酸、乳铁蛋白、砷剂、维生素甲类化合物、亚硒酸钠、某些中草药等的近期研究现状进行综述。     

Hematologic and immunologic responses in common marmosets (Callithrix jacchus) infected with Plasmodium knowlesi and Epstein-Barr virus

The hematologic and immunologic responses to infection with either the Epstein-Barr virus alone or infection with Epstein-Barr virus and Plasmodium knowlesi were studied using common marmosets (Callithrix jacchus). The assays performed included complete blood cell counts, determinations of natural killer cell activity, and determinations of antibody titers to Epstein-Barr virus early antigen, virus capsid antigen and the nuclear antigen. While no animal showed signs of lymphoproliferative disease, it was found that animals infected with Epstein-Barr virus became positive for early antigen, virus capsid antigen and nuclear antigen at low levels. No difference in antibody titers between Epstein-Barr virus infected animals and co-infected animals was observed. An increase also was found in the number of leukocytes in all groups, and an increase in natural killer cells following infection with Epstein-Barr virus. Some depression in natural killer cells was observed in the co-infected animals when compared to Epstein-Barr virus infected animals.     

EB病毒及其疫苗的研究进展

EB病毒广泛存在于人群中,它的潜伏感染与多种疾病密切相关,包括鼻咽癌等恶性肿瘤,研制疫苗用于EB病毒相关疾病的预防和治疗十分必要。本综述了EB病毒的结构及基因表达特点、EB病毒潜伏期感染基因表达及潜伏期基因产物的功能,以及研制EB病毒疫苗的靶抗原的选择。     

Epstein-Barr virus infection and sporadic breast cancer risk: a meta-analysis

Background

A large number of epidemiological studies have evaluated the association between Epstein-Barr virus infection and breast carcinoma risk but results have been inconsistent.

Methodology

Research using the polymerase chain reaction technique for detecting the Epstein-Barr virus was selected; 24 studies and 1535 cases were reviewed. Information on the study populations, sample types, publication calendar period and histological types of breast carcinoma were collected. An unconditional logistic regression model was used to analyze potential parameters related to the Epstein-Barr virus prevalence. A Kappa test was used to evaluate the consistency in detecting different Epstein-Barr virus DNA regions. Nine studies that included control groups and 1045 breast cancer cases were adopted in this meta-analysis.

Conclusions

We found that 29.32% of the patients with breast carcinoma were infected with the Epstein-Barr virus. The prevalence of Epstein-Barr was highest in Asia (35.25%) and lowest in the USA (18.27%). Statistical analysis revealed a trend that showed lobular breast carcinoma might have the strongest association with Epstein-Barr virus infection. This meta-analysis showed a significant increase in breast malignancy risk in patients testing positive for the Epstein-Barr virus (OR = 6.29, 95% CI = 2.13–18.59). This result suggests that an Epstein-Barr virus infection is statistically associated with increased breast carcinoma risk.     

Epstein-Barr virus RNA. VIII. Viral RNA in permissively infected B95-8 cells

More than 50 RNAs expressed by Epstein-Barr virus late in productive infection have been identified. B95-8-infected cells were induced to a relatively high level of permissive infection with the tumor promotor 12-O-tetradecanoylphorbol-13-acetate. Polyadenylated RNAs were extracted from the cell cytoplasm, separated by size on formaldehyde gels, transferred to nitrocellulose, and hybridized to labeled recombinant Epstein-Barr virus DNA fragments. Comparison of RNAs from induced cultures with RNAs from induced cultures also treated with phosphonoacetic acid to inhibit viral DNA synthesis identifies two RNA classes: a persistent early class of RNAs whose abundance is relatively resistant to viral DNA synthesis inhibition and a late class of RNAs whose abundance is relatively sensitive to viral DNA synthesis inhibition. The persistent early and late RNAs are not clustered but are intermixed and scattered through most of segments UL and US. The cytoplasmic polyadenylated RNAs expressed during latent infection were not detected in productively infected cells, indicating that different classes of viral RNA are associated with latent and productive infection. Non-polyadenylated small RNAs originally identified in cells latently infected with Epstein-Barr virus are expressed in greater abundance in productively infected cells and are part of the early RNA class.     

Proteomic profiling of EBNA1-host protein interactions in latent and lytic Epstein-Barr virus infections

The Epstein-Barr nuclear antigen 1 (EBNA1) protein of Epstein-Barr virus (EBV) is expressed in both latent and lytic modes of EBV infection and contributes to EBV-associated cancers. Using a proteomics approach, we profiled EBNA1-host protein interactions in nasopharyngeal and gastric carcinoma cells in the context of latent and lytic EBV infection. We identified several interactions that occur in both modes of infection, including a previously unreported interaction with nucleophosmin and RNA-mediated interactions with several heterogeneous ribonucleoproteins (hnRNPs) and La protein.     

Induction of Epstein-Barr virus nuclear antigens.

Lymphocytes were infected with the QIMR-WIL strain of Epstein-Barr virus, and the induction of Epstein-Barr virus-associated nuclear antigens was determined by using the protein immunoblot. There was a temporal increase in six antigens, with Epstein-Barr nuclear antigen 2 being detected 1 day after infection. The appearance of these antigens was shown to be independent of cellular DNA synthesis.     

Inhibition of Epstein-Barr virus-mediated capping of CD21/CR2 by alpha interferon (IFN-alpha): immediate antiviral activity of IFN-alpha during the early phase of infection.

Early events of human B-lymphocyte infection by Epstein-Barr virus involve the virus binding to CD21, capping, and subsequent internalization of the virus-receptor complex. We show here that alpha interferon (IFN-alpha) inhibits the capping of Epstein-Barr virus-CD21 complexes. Synthetic peptides with the CD21 binding motif of IFN-alpha mimic IFN-alpha activity, suggesting that this effect may be mediated by IFN-alpha-CD21 interaction. Our findings demonstrate a novel and immediate mechanism of IFN-alpha action.     

T-cell memory: lessons from Epstein-Barr virus infection in man

Epstein-Barr virus offers an ideal opportunity to follow the human T-cell response to a virus infection over time from its acute primary phase, as seen in infectious mononucleosis patients, into the memory phase that accompanies life-long virus persistence. Here we review recent evidence on the development and maturation of cytotoxic T-cell memory using this viral system.     

EB病毒与子宫颈癌发病的关系

目的 分析EB病毒感染与子宫颈的关系及其对抑癌基因p53表达的影响,探讨EB病毒的致癌机制。方法 采用免疫组织化学S-P法,分别检测59例宫颈鳞癌,19例正常宫颈组织的EB病毒（Epstein-Barr virus,EBV）及抑癌基因p53蛋白的表达情况,并进一步分析宫颈癌组织EBV感染与抑癌基因p53表达的关系。结果 EBV阳性表达率在宫颈癌及正常宫颈组分别为64．4％和21．1％,2组间差异有显著性（P〈0．05）;p53在宫颈癌组织中的阳性表达率为64．4％,明显高于正常宫颈组26．3％,（P〈0．05）。EBV感染与非感染的宫颈癌组织中,p53的阳性表达率分别为78．9％与38．1％,2组间差异有显著性（P〉0．05）。结论 EBV病毒感染与宫颈癌的发病密切相关,但其机制可能是通过影响抑癌基因P53表达而致癌。     

DNA-mediated immunization of glycoprotein 350 of Epstein-Barr virus induces the effective humoral and cellular immune responses against the antigen

Epstein-Barr virus (EBV) is a human pathogen that is involved in numerous diseases and tumors. Since the EBV infection occurs in the early ages of life, and most of the population is subsequently exposed to EBV, the conventional method of vaccination to induce the prophylactic immunity cannot be considered effective in coping with the virus infection. In this study, we tested whether the injection of a plasmid vector that contained the gene for glycoprotein 350 (gp350), which had been identified as a ligand for virus' adsorption and a target for virus neutralizing antibodies, could induce effective immune responses against the antigen. As a result, the injection of the constructed plasmid vector into mice induced the production of gp350-specific antibodies. A major isotype of the gp350-specific antibodies was IgG1. The antibodies efficiently mediated the antibody-dependent cellular cytotoxicity against the cells expressing the gp350 antigen. In addition, the injection of the constructed plasmid vector stimulated the precursor T cell population that was specific to the gp350 antigen. In addition, gp350-specific cytotoxic T lymphocytes were efficiently stimulated by the injection of the constructed plasmid vector. These results suggested that the injection of the plasmid vector, containing the gp350 gene of Epstein-Barr virus, could be one of the most effective ways to induce both prophylactic and therapeutic vaccinations against the virus infection.     

Effects of virally expressed interleukin-10 on vaccinia virus infection in mice.

To investigate the in vivo role of interleukin-10 (IL-10) in viral infection, we compared infections with a recombinant vaccinia virus (VV) expressing IL-10 (VV-IL10) under control of the VV P7.5 promoter and a control virus (VV-beta gal) in normal and severe combined immunodeficient mice. In normal mice, VV-IL10 infection resulted in less natural killer cell activity at 3 days postinfection and less VV-specific cytotoxic T-cell activity at 6 or 7 days postinfection than VV-beta gal infection. However, the use of dermal scarification or intraperitoneal, intranasal, or intracerebral inoculation into immunocompetent mice resulted in no difference between VV-IL10 and VV-beta gal in visible lesions, mortality, protective immunity to a 100-fold lethal VV challenge, or VV-specific antibody response. In the immunodeficient mice, VV-IL10 infection resulted in greater natural killer cell activity and lower virus replication than VV-beta gal infection. These in vivo effects were subtler and more complex than had been anticipated. From the VV-IL10 murine model, the Epstein-Barr virus-encoded homolog of human IL-10, BCRF1, may provide a selective advantage by blunting the early human natural killer cell and cytotoxic T-cell responses so that Epstein-Barr virus can establish a well-contained latent infection in B lymphocytes.     

Differential effects of acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine on herpes simplex virus and Epstein-Barr virus in a dually infected human lymphoblastoid cell line.

We investigated the effects of acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) on a lymphoblastoid cell line dually infected with Epstein-Barr virus and herpes simplex virus (HSV) type 1. The numbers of Epstein-Barr virus genomes were reduced during 70 days of treatment with either drug. Both drugs suppressed HSV replication in a dose-related manner. In the continued presence of the drugs, HSV developed resistance, rapidly to acyclovir and much more slowly to 30 microM DHPG. Analysis of HSV glycoprotein C production and viral DNA showed that treatment with 100 microM DHPG eliminated HSV production, curing the cell line of HSV persistent infection.     

Control mechanisms of Epstein-Barr virus persistence

Epstein-Barr virus (EBV), a gammaherpesvirus widespread in all human populations, establishes an asymptomatic persistent infection in the majority of individuals. This review briefly summarizes what is known about the complex interactions between the virus and its host, with particular emphasis on the immune mechanisms that are involved in controlling persistent infection. EBV also persists in the malignant cells of a number of human tumors. The possible mechanisms by which these cells might avoid virus-specific immune responses and the potential for adapting these responses to clear the tumor are also discussed.     

Epstein-Barr病毒相关淋巴瘤的研究进展

Epstein-Barr病毒（Epstein-Barr virus,EBV）是第1个被发现与人类肿瘤发生相关的病毒,且越来越多的数据表明其感染与某些淋巴瘤的发生发展、治疗及预后密切相关。近年来免疫治疗手段发展迅速,但EBV阳性淋巴瘤的治疗目前主要仍以放化疗为基础,结合抗病毒药物。因此,加强EBV及其相关淋巴瘤的研究,寻找有效预防或治疗EBV感染的方法,将有望改善EBV阳性淋巴瘤患者的预后。     

Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate-early gene after primary infection of B lymphocytes

We demonstrate here that the Epstein-Barr virus (EBV) BZLF1 gene, a switch from latent infection to lytic infection, is expressed as early as 1.5 h after EBV infection in Burkitt's lymphoma-derived, EBV-negative Akata and Daudi cells and primary B lymphocytes. Since BZLF1 mRNA is expressed even when the cells are infected with EBV in the presence of anisomycin, an inhibitor of protein synthesis, its expression does not require prerequisite protein synthesis, indicating that BZLF1 is expressed as an immediate-early gene following primary EBV infection of B lymphocytes.     

Production of 22 nm HBsAG particles by human lymphocytes infected with a recombinant vaccinia virus containing the coding sequence for hepatitis B virus surface antigen.

To examine the possible role of lymphocytes in the course of hepatitis B virus infection, we studied peripheral blood lymphocytes and Epstein-Barr virus transformed B-cells for their capability to produce hepatitis B virus gene products. Infection of these cells with a recombinant vaccinia virus containing the hepatitis B virus surface antigen resulted in the production and secretion of hepatitis B virus surface antigen shortly after infection reaching a peak after three days. When the supernatants of the cells were analyzed on density gradients, a peak of reactivity for hepatitis B virus surface antigen was reached at 1.21 g/cm3. Electron microscopy revealed the presence of spherical and filamentous HBsAg particles. These findings show that human lymphocytes are capable of producing hepatitis B virus surface antigen.     

Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses.

Infection of rodent cells by ecotropic type C retroviruses requires the expression of a cationic amino acid transporter composed of multiple membrane-spanning domains. By exchanging portions of cDNAs encoding the permissive mouse and nonpermissive human transporters and examining their abilities to specify virus infection upon expression in human 293 cells, we have identified the amino acid residues in the extracellular loop connecting the fifth and sixth membrane-spanning segments of the mouse transporter that are required for both envelope gp70 binding and infection. These findings strongly suggest that the role of the mouse transporter in determining infection is to provide an envelope-binding site. This role is analogous to those of host membrane proteins composed of a single membrane-spanning domain that serve as binding proteins or receptors for other enveloped viruses such as human immunodeficiency virus, Epstein-Barr virus, and murine and human coronaviruses.