Detection of lymphocytes productively infected with Epstein–Barr virus in non-neoplastic tonsils

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1211-1216 ◽  
Author(s):  
Tetsuya Ikeda ◽  
Ryo Kobayashi ◽  
Manabu Horiuchi ◽  
Yoshifumi Nagata ◽  
Makoto Hasegawa ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Immune Surveillance ◽  
Lymphoid Tissues ◽  
Healthy Individuals ◽  
Barr Virus ◽  
Multiple Copies ◽  
The Face ◽  
Infected Cells ◽  
Epstein Barr

Epstein–Barr virus (EBV) persists for life in the infected host. Little is known about EBV reactivation and regulation of virus persistence in healthy individuals. We examined tonsils of chronic tonsillitis patients to detect EBV transcripts, EBV genomes and lytic proteins. LMP1 transcripts were observed in 11 of 15 specimens and BZLF1 transcripts were detected in six. Multiple copies of EBV genome equivalents per cell, and ZEBRA- and viral capsid antigen-positive cells were also detected in tonsillar lymphocytes. These results indicate that EBV productively infected cells may survive in the face of immune surveillance in the tonsils. Thus, EBV replication may occur in tonsillar lymphocytes, and tonsillar lymphoid tissues may play a role in the maintenance of EBV load in vivo.

scholarly journals Methylation of the Epstein-Barr Virus Genome in Normal Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4480-4484 ◽  
Author(s):  
Keith D. Robertson ◽  
Richard F. Ambinder
Keyword(s):  
B Cells ◽  
Epstein Barr Virus ◽  
Defense Mechanism ◽  
Immune Surveillance ◽  
Virus Genome ◽  
Barr Virus ◽  
The Face ◽  
Ebv Dna ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) latent infection in B cells persists over years or decades despite a sustained cytotoxic immune response to viral antigens. We present data that methylated EBV DNA can be detected in the normal lymphocytes of healthy volunteers. Whereas methylation of foreign DNA has been recognized as a potential cellular defense mechanism, methylation of EBV DNA may be an essential part of the virus life cycle in vivo, explaining the persistence of virus-infected B cells in the face of immune surveillance. Methylation of the C promoter helps to prevent expression of the immunodominant antigens expressed from this promoter. First recognized in tumors, methylation-associated evasion of immune surveillance is not an aberration restricted to tumor tissue but is detected in normal EBV-infected lymphocytes. Methylation of the viral genome in latency also provides an explanation for the CpG suppression associated with EBV but not other large DNA viruses.

scholarly journals Methylation of the Epstein-Barr Virus Genome in Normal Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4480-4484 ◽  
Author(s):  
Keith D. Robertson ◽  
Richard F. Ambinder
Keyword(s):  
B Cells ◽  
Epstein Barr Virus ◽  
Defense Mechanism ◽  
Immune Surveillance ◽  
Virus Genome ◽  
Barr Virus ◽  
The Face ◽  
Ebv Dna ◽  
Epstein Barr

Epstein-Barr virus (EBV) latent infection in B cells persists over years or decades despite a sustained cytotoxic immune response to viral antigens. We present data that methylated EBV DNA can be detected in the normal lymphocytes of healthy volunteers. Whereas methylation of foreign DNA has been recognized as a potential cellular defense mechanism, methylation of EBV DNA may be an essential part of the virus life cycle in vivo, explaining the persistence of virus-infected B cells in the face of immune surveillance. Methylation of the C promoter helps to prevent expression of the immunodominant antigens expressed from this promoter. First recognized in tumors, methylation-associated evasion of immune surveillance is not an aberration restricted to tumor tissue but is detected in normal EBV-infected lymphocytes. Methylation of the viral genome in latency also provides an explanation for the CpG suppression associated with EBV but not other large DNA viruses.

scholarly journals Acyclovir Improves the Efficacy of Chemoradiation in Nasopharyngeal Cancer Containing the Epstein Barr Virus Genome

2020 ◽  
Author(s):  
Aditya Thandoni ◽  
Andrew Zloza ◽  
Devora Schiff ◽  
Malay Rao ◽  
Kwok-wai Lo ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Treatment Options ◽  
Immune Surveillance ◽  
Nasopharyngeal Cancer ◽  
Standard Of Care ◽  
Virus Genome ◽  
Barr Virus ◽  
Standard Of Care Treatment ◽  
Epstein Barr

AbstractNasopharyngeal carcinoma (NPC) is a malignancy endemic to East Asia and is caused by Epstein-Barr Virus (EBV)-mediated cancerous transformation of epithelial cells. The standard of care treatment for NPC involves radiation and chemotherapy. While treatment outcomes continue to improve, up to 50% of patients can be expected to recur by five years, and additional innovative treatment options are needed. We posit that a potential way to do this is by targeting the underlying cause of malignant transformation, namely EBV. One method by which EBV escapes immune surveillance is by undergoing latent phase replication, during which EBV expression of immunogenic proteins is reduced. However, chemoradiation is known to drive conversion of EBV from a latent to a lytic phase. This creates an opportunity for the targeting of EBV-infected cells utilizing anti-viral drugs. Indeed, we found that combining acyclovir with cisplatin and radiation significantly decreases the viability of the EBV-infected C666-1 cell line. Western blot quantification revealed a resultant increase of thymidine kinase (TK) and apoptosis-inducing mediators, cleaved PARP (cPARP) and phosphorylated ERK (pERK). These studies suggest that the addition of anti-viral drugs to frontline chemoradiation may improve outcomes in patients treated for EBV-related NPC and future in vivo and clinical studies are needed.

LYDMA-antigens and Immunity against EBV-infected Cells Epstein-Barr Virus as a Model for the Study of Host-infection Interaction

1987 ◽  
Vol 2 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Maria L. Villa ◽  
Emilio Bombardieri
Keyword(s):  
Transcriptional Activation ◽  
Epstein Barr Virus ◽  
Dna Viruses ◽  
Barr Virus ◽  
Good Potential ◽  
Infected Cells ◽  
Membrane Antigens ◽  
Epstein Barr ◽  
Host Infection

Molecular biology has shown that DNA viruses carry their own transforming genes, unlike RNA viruses (retrovirus), which use cellular “oncogenes”. Some of the products of transforming viral genes are very good potential targets for immune defence. Epstein-Barr virus (EBV) immortalization is linked to the transcriptional activation of some latently transcribed regions; the lymphocyte-determined membrane antigens (LYDMA), the product of one of these regions, are the T-cell's chosen target. EBV-induced immortalization may therefore be free from any malignant consequence as long as immortalized clones are suppressed by immunosurveillance. In vivo, LYDMA-positive clones may be susceptible to immune control; LYDMA-negative clones can transform to neoplastic cells

scholarly journals Oncogenic Properties of the EBV ZEBRA Protein

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1479
Author(s):  
Diego Germini ◽  
Fatimata Bintou Sall ◽  
Anna Shmakova ◽  
Joëlle Wiels ◽  
Svetlana Dokudovskaya ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Host Proteins ◽  
Barr Virus ◽  
Infected Cells ◽  
Functional Features ◽  
Epstein Barr ◽  
Human Herpesviruses ◽  
Transcriptional Transactivator

Epstein Barr Virus (EBV) is one of the most common human herpesviruses. After primary infection, it can persist in the host throughout their lifetime in a latent form, from which it can reactivate following specific stimuli. EBV reactivation is triggered by transcriptional transactivator proteins ZEBRA (also known as Z, EB-1, Zta or BZLF1) and RTA (also known as BRLF1). Here we discuss the structural and functional features of ZEBRA, its role in oncogenesis and its possible implication as a prognostic or diagnostic marker. Modulation of host gene expression by ZEBRA can deregulate the immune surveillance, allow the immune escape, and favor tumor progression. It also interacts with host proteins, thereby modifying their functions. ZEBRA is released into the bloodstream by infected cells and can potentially penetrate any cell through its cell-penetrating domain; therefore, it can also change the fate of non-infected cells. The features of ZEBRA described in this review outline its importance in EBV-related malignancies.

scholarly journals The Intersection of Epstein-Barr Virus with the Germinal Center

2009 ◽  
Vol 83 (8) ◽  
pp. 3968-3976 ◽  
Author(s):  
Jill E. Roughan ◽  
David A. Thorley-Lawson
Keyword(s):  
B Cells ◽  
Germinal Center ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latently Infected ◽  
Infected Cells ◽  
Epstein Barr ◽  
Transcription Program

ABSTRACT The current model of Epstein-Barr virus (EBV) infection and persistence in vivo proposes that EBV uses the germinal center (the GC model) to establish a quiescent latent infection in otherwise-normal memory B cells. However, the evidence linking EBV-infected cells and the GC is only indirect and limited. Therefore, a key portion of the model, that EBV-infected cells physically reside and participate in GCs, has yet to be verified. Furthermore, recent experiments suggested that upon infection of GC cells the viral growth latency transcription program is dominant and GC functionality and phenotype are ablated, i.e., EBV infection is not consistent with GC function. In this study we show that in vivo, EBV-infected B cells in the tonsils retain expression of functional and phenotypic markers of GC cells, including bcl-6 and AID. Furthermore, these cells are physically located in the GC and express a restricted form of latency, the default latency program. Thus, the EBV default latency transcription program, unlike the growth latency program, is consistent with the retention of GC functionality in vivo. This work verifies key components of the GC model of EBV persistence and suggests that EBV and the GC can interact to produce the latently infected memory cells found in the periphery. Furthermore, it identifies latently infected GC B cells as a potential pathogenic nexus for the development of the EBV-positive, GC-associated lymphomas Hodgkin's disease and Burkitt's lymphoma.

scholarly journals Epstein-Barr Virus Small RNA (EBER) Genes: Differential Regulation during Lytic Viral Replication

1998 ◽  
Vol 72 (11) ◽  
pp. 9323-9328 ◽  
Author(s):  
Norbert Greifenegger ◽  
Michael Jäger ◽  
Leoni A. Kunz-Schughart ◽  
Hans Wolf ◽  
Fritz Schwarzmann
Keyword(s):  
Viral Replication ◽  
Epstein Barr Virus ◽  
Transcriptional Activity ◽  
Lytic Replication ◽  
Early Event ◽  
Transcriptional Level ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr

ABSTRACT In every latently Epstein-Barr virus-infected cell the viral genes EBER-1 and EBER-2 are transcribed by polymerase III. In lytically infected cells in vivo the EBER genes could not be detected. However, in cell culture downregulation could not be confirmed, and hence the relevance of this shutdown to the replication of the virus was not clear. We assayed the transcriptional activity of the EBER genes by nuclear run-on assays with enriched lytically infected cells and demonstrated that EBER-1 and EBER-2 are differentially downregulated on the transcriptional level during the switch to lytic viral replication. This downregulation was an early event during the lytic replication of the virus.

Studies of Epstein-Barr Virus Antigens Using Immunoperoxidase and Immunofluorescence Techniques

1975 ◽  
Vol 33 ◽  
pp. 342-343
Author(s):  
R. Stephens ◽  
K. Traul ◽  
D. Woolf ◽  
P. Gaudreau
Keyword(s):  
Electron Microscopy ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
If Technique ◽  
Infected Cells ◽  
Virus Antigens ◽  
Epstein Barr ◽  
Virus Capsid Antigen ◽  
Antigen Reactivity

A number of antigens have been found associated with persistent EBV infections of lymphoblastoid cells. Identification and localization of these antigens were principally by immunofluorescence (IF) techniques using sera from patients with nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL), and infectious mononucleosis (IM). Our study was mainly with three of the EBV related antigens, a) virus capsid antigen (VCA), b) membrane antigen (MA), and c) early antigens (EA) using immunoperoxidase (IP) techniques with electron microscopy (EM) to elucidate the sites of reactivity with EBV and EBV infected cells.Prior to labeling with horseradish peroxidase (HRP), sera from NPC, IM, and BL cases were characterized for various reactivities by the indirect IF technique. Modifications of the direct IP procedure described by Shabo and the indirect IP procedure of Leduc were made to enhance penetration of the cells and preservation of antigen reactivity.

scholarly journals EBV-LMP1 promotes radioresistance by inducing protective autophagy through BNIP3 in nasopharyngeal carcinoma

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
San Xu ◽  
Zhuan Zhou ◽  
Xingzhi Peng ◽  
Xuxiu Tao ◽  
Peijun Zhou ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Crucial Role ◽  
Epstein Barr Virus ◽  
Interacting Protein ◽  
Multiple Tumors ◽  
Barr Virus ◽  
Signaling Axis ◽  
Epstein Barr ◽  
Adenovirus E1b

AbstractStudies have indicated that dysfunction of autophagy is involved in the initiation and progression of multiple tumors and their chemoradiotherapy. Epstein–Barr virus (EBV) is a lymphotropic human gamma herpes virus that has been implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). EBV encoded latent membrane protein1 (LMP1) exhibits the properties of a classical oncoprotein. In previous studies, we experimentally demonstrated that LMP1 could increase the radioresistance of NPC. However, how LMP1 contributes to the radioresistance in NPC is still not clear. In the present study, we found that LMP1 could enhance autophagy by upregulating the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3). Knockdown of BNIP3 could increase the apoptosis and decrease the radioresistance mediated by protective autophagy in LMP1-positive NPC cells. The data showed that increased BNIP3 expression is mediated by LMP1 through the ERK/HIF1α signaling axis, and LMP1 promotes the binding of BNIP3 to Beclin1 and competitively reduces the binding of Bcl-2 to Beclin1, thus upregulating autophagy. Furthermore, knockdown of BNIP3 can reduce the radioresistance promoted by protective autophagy in vivo. These data clearly indicated that, through BNIP3, LMP1 induced autophagy, which has a crucial role in the protection of LMP1-positive NPC cells against irradiation. It provides a new basis and potential target for elucidating LMP1-mediated radioresistance.

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