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Viruses
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The Roles of EBV Infection in the Internal and External...
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The Roles of EBV Infection in the Internal and External Environment of EBV-Related Tumors

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11923

Special Issue Editors

Dr. Xiaoming Lyu

E-Mail Website
Guest Editor
1. The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
2. Department of Laboratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
Interests: interaction between EBV and host cells, especially the impact of reactivation of EBV on the development; diagnosis; treatment and prognosis of nasopharyngeal carcinoma
Special Issues, Collections and Topics in MDPI journals
Dr. Chi Man Tsang

E-Mail Website
Guest Editor
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: nasopharyngeal carcinoma; Epstein–Barr virus; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Epstein-Barr virus (EBV) belongs to the γ subfamily of the family Herpesviridae. It has the property of phagocytosing B lymphocytes, and can establish latent infection in B lymphocytes and stimulate the proliferation and transformation of cells. The infection rate in the population is more than 90%. Although most EBV-infected individuals remain asymptomatic, EBV infection increases the risk of developing various malignancies. In 1997, the World Health Organization's International Agency for Research on Cancer (LARC) report classified EBV as being among carcinogens. EBV is associated with an increasing number of human tumors, including post-transplant lymphoproliferative disease (PTLD), Hodgkin's disease (HD), Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC) and approximately 10–15% of gastric cancers, etc. However, its role in these malignancies has not been fully elucidated. The effects of EBV on tumor cells and the tumor microenvironment at different stages of infection are obvious and worth exploring.

Dr. Xiaoming Lyu
Dr. Chi Man Tsang
Guest Editors

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Keywords

  • Epstein-Barr virus (EBV)
  • EBV-associated tumors
  • oncogenesis
  • tumor progressiveness
  • cancer microenvironment

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Published Papers (4 papers)

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Research

22 pages, 17233 KiB  
Article
EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma
by Tengteng Ding, Yuanbin Zhang, Zhixuan Ren, Ying Cong, Jingyi Long, Manli Peng, Oluwasijibomi Damola Faleti, Yinggui Yang, Xin Li and Xiaoming Lyu
Viruses 2023, 15(9), 1915; https://doi.org/10.3390/v15091915 - 12 Sep 2023
Cited by 1 | Viewed by 1736
Abstract
This study aimed to develop a model using Epstein–Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected [...] Read more.
This study aimed to develop a model using Epstein–Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis. These 25 genes were used to classify NPC into two subtypes, and six genes (C16orf54, CD27, CD53, CRIP1, RARRES3, and TBC1D10C) were found to be hub genes in NPC related to immune infiltration and cell cycle regulation. It was shown that these genes could be used to predict the prognosis of NPC, with functions related to tumor proliferation and immune infiltration, making them potential therapeutic targets. The findings of this study could aid in the development of screening and prognostic methods for NPC based on EBV-related features. Full article
(This article belongs to the Special Issue The Roles of EBV Infection in the Internal and External Environment of EBV-Related Tumors)
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20 pages, 3385 KiB  
Article
IL-8 Secreted by Gastric Epithelial Cells Infected with Helicobacter pylori CagA Positive Strains Is a Chemoattractant for Epstein–Barr Virus Infected B Lymphocytes
by Diana A. Domínguez-Martínez, José I. Fontes-Lemus, Alejandro García-Regalado, Ángel Juárez-Flores and Ezequiel M. Fuentes-Pananá
Viruses 2023, 15(3), 651; https://doi.org/10.3390/v15030651 - 28 Feb 2023
Cited by 5 | Viewed by 2924
Abstract
Helicobacter pylori and EBV are considered the main risk factors in developing gastric cancer. Both pathogens establish life-lasting infections and both are considered carcinogenic in humans. Different lines of evidence support that both pathogens cooperate to damage the gastric mucosa. Helicobacter pylori CagA [...] Read more.
Helicobacter pylori and EBV are considered the main risk factors in developing gastric cancer. Both pathogens establish life-lasting infections and both are considered carcinogenic in humans. Different lines of evidence support that both pathogens cooperate to damage the gastric mucosa. Helicobacter pylori CagA positive virulent strains induce the gastric epithelial cells to secrete IL-8, which is a potent chemoattractant for neutrophils and one of the most important chemokines for the bacterium-induced chronic gastric inflammation. EBV is a lymphotropic virus that persists in memory B cells. The mechanism by which EBV reaches, infects and persists in the gastric epithelium is not presently understood. In this study, we assessed whether Helicobacter pylori infection would facilitate the chemoattraction of EBV-infected B lymphocytes. We identified IL-8 as a powerful chemoattractant for EBV-infected B lymphocytes, and CXCR2 as the main IL-8 receptor whose expression is induced by the EBV in infected B lymphocytes. The inhibition of expression and/or function of IL-8 and CXCR2 reduced the ERK1/2 and p38 MAPK signaling and the chemoattraction of EBV-infected B lymphocytes. We propose that IL-8 at least partially explains the arrival of EBV-infected B lymphocytes to the gastric mucosa, and that this illustrates a mechanism of interaction between Helicobacter pylori and EBV. Full article
(This article belongs to the Special Issue The Roles of EBV Infection in the Internal and External Environment of EBV-Related Tumors)
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14 pages, 2554 KiB  
Article
Comprehensive Profiling of EBV Gene Expression and Promoter Methylation Reveals Latency II Viral Infection and Sporadic Abortive Lytic Activation in Peripheral T-Cell Lymphomas
by Joanna W. Y. Ho, Lili Li, Kai Yau Wong, Gopesh Srivastava and Qian Tao
Viruses 2023, 15(2), 423; https://doi.org/10.3390/v15020423 - 2 Feb 2023
Cited by 9 | Viewed by 2641
Abstract
Epstein-Barr virus (EBV) latency patterns are well defined in EBV-associated epithelial, NK/T-cell, and B-cell malignancies, with links between latency stage and tumorigenesis deciphered in various studies. In vitro studies suggest that the oncogenic activity of EBV in T-cells might be somewhat different from [...] Read more.
Epstein-Barr virus (EBV) latency patterns are well defined in EBV-associated epithelial, NK/T-cell, and B-cell malignancies, with links between latency stage and tumorigenesis deciphered in various studies. In vitro studies suggest that the oncogenic activity of EBV in T-cells might be somewhat different from that in EBV-tropic B lymphoid cells, prompting us to study this much less investigated viral gene expression pattern and its regulation in nine EBV+ peripheral T-cell lymphoma (PTCL) biopsies. Using frozen specimens, RT-PCR showed 6/7 cases with a latency II pattern of EBV gene expression. Analyses of EBNA1 promoter usage and CpG methylation status in these six cases showed that only Qp was used, while Cp, Wp, and Fp were all silent. However, the remaining case showed an exceptionally unique latency III type with lytic activation, as evidenced by EBV lytic clonality and confirmed by the full usage of Cp and Qp as well as weakly lytic Fp and Wp, fully unmethylated Cp and marginally unmethylated Wp. Further immunostaining of the eight cases revealed a few focally clustered LMP1+ cells in 7/8 cases, with rare isolated LMP1+ cells detected in another case. Double immunostaining confirmed that the LMP1+ cells were of the T-cell phenotype (CD3+). In 6/8 cases, sporadically scattered Zta+ cells were detected. Double staining of EBER-ISH with T-cell (CD45RO/UCHL1) or B-cell (CD20) markers confirmed that the vast majority of EBER+ cells were of the T-cell phenotype. Predominant type-A EBV variant and LMP1 30-bp deletion variant were present, with both F and f variants detected. In summary, the EBV gene expression pattern in PTCL was found to be mainly of latency II (BART+EBNA1(Qp)+LMP1+LMP2A+BZLF1+), similar to that previously reported in EBV-infected nasopharyngeal epithelial, NK/T-cell, and Hodgkin malignancies; however, fully lytic infection could also be detected in occasional cases. Rare cells with sporadic immediate-early gene expression were commonly detected in PTCL. These findings have implications for the future development of EBV-targeting therapeutics for this cancer. Full article
(This article belongs to the Special Issue The Roles of EBV Infection in the Internal and External Environment of EBV-Related Tumors)
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17 pages, 4322 KiB  
Article
Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion
by Mikhail Salnikov, Martin A. Prusinkiewicz, Sherman Lin, Farhad Ghasemi, Matthew J. Cecchini and Joe S. Mymryk
Viruses 2023, 15(1), 176; https://doi.org/10.3390/v15010176 - 7 Jan 2023
Cited by 9 | Viewed by 3143
Abstract
Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with 10% of all gastric cancers (GCs) and 1.5% of all human cancers. EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology, treatment response, and patient [...] Read more.
Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with 10% of all gastric cancers (GCs) and 1.5% of all human cancers. EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology, treatment response, and patient prognosis. However, the tumor immune landscape of EBVaGC has not been well explored. In this study, a systemic and comprehensive analysis of gene expression and immune landscape features was performed for both EBVaGC and EBVnGC. EBVaGCs exhibited many aspects of a T cell-inflamed phenotype, with greater T and NK cell infiltration, increased expression of immune checkpoint markers (BTLA, CD96, CTLA4, LAG3, PD1, TIGIT, and TIM3), and multiple T cell effector molecules in comparison with EBVnGCs. EBVaGCs also displayed a higher expression of anti-tumor immunity factors (PDL1, CD155, CEACAM1, galectin-9, and IDO1). Six EBV-encoded miRNAs (miR-BARTs 8-3p, 9-5p, 10-3p, 22, 5-5p, and 14-3p) were strongly negatively correlated with the expression of immune checkpoint receptors and multiple markers of anti-tumor immunity. These profound differences in the tumor immune landscape between EBVaGCs and EBVnGCs may help explain some of the observed differences in pathological and clinical outcomes, with an EBV-positive status possibly being a potential biomarker for the application of immunotherapy in GC. Full article
(This article belongs to the Special Issue The Roles of EBV Infection in the Internal and External Environment of EBV-Related Tumors)
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