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Microorganisms
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Recent Advances in Understanding Epstein-Barr Virus
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Recent Advances in Understanding Epstein-Barr Virus

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 20137

Special Issue Editors

Prof. Dr. Hironori Yoshiyama

E-Mail Website
Guest Editor
Department of Microbiology, Shimane University Faculty of Medicine, Shimane 693-8501, Japan
Interests: microbial pathogenesis (HIV, EBV, H. pylori); infection associated cancers
Special Issues, Collections and Topics in MDPI journals
Prof. Teru Kanda

E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Medicine, Tohoku Medical Pharmaceutical University, Sendai, Japan
Interests: EBV; viral genome sequencing; reverse genetics; cancer biology; cell biology

Special Issue Information

Dear Colleagues,

The Epstein-Barr virus (EBV) is a human gamma-herpesvirus and more than 90% of population is infected with the virus. EBV infects with oropharyngeal naïve B lymphocytes through saliva then spread to the adjacent B lymphocytes and epithelial cells. Immunological maturation of infected host divides initial infections to asymptomatic infection in infancy and infectious mononucleosis in adolescence. The initial productive lytic infection will shift to persistent latent infection, where limited viral transcripts are expressed to support persistent infection. In most of the cases, EBV associates with the infected person without any symptoms during the person’s life. Primarily resting memory B lymphocytes in peripheral blood provide a permanent reservoir for the virus. However, EBV sometimes shifts from latent to lytic infection in association with local or systemic immunological suppressions. The life long persistence and regional activation may induce oncogenic activation of infected cells in some persons. Thus, EBV sometimes associates with lymphoid or epithelial cancers (Burkitt’s lymphoma, Hodgkin lymphoma, NK/T lymphoma, nasopharyngeal carcinoma, EBV-associated gastric cancers, and so on). EBV-specific immunity controls shift from lytic to latent infection as well as formation of EBV-associated cancers. In order to understand the complex interactions between EBV and host, this Special Issue will collect reviews or original research articles regarding recent advances in Epstein-Barr virus research, which is spanning from basic biology to potential clinical implications.

Prof. Hironori Yoshiyama
Prof. Teru Kanda
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • EBV
  • Helicobacter pylori
  • micro RNA
  • infection-associated cancers
  • immunodeficiency
  • viral genome sequencing
  • reverse genetics
  • cancer biology
  • cell biology

Published Papers (4 papers)

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Research

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9 pages, 2248 KiB  
Article
Clinicopathologic Characteristics of Epstein–Barr Virus-Associated Gastric Cancer Over the Past Decade in Japan
by Ayaka Yanagi, Jun Nishikawa, Kanami Shimokuri, Takuya Shuto, Tatsuya Takagi, Fumiya Takagi, Yuki Kobayashi, Misa Yamamoto, Osamu Miura, Hideo Yanai, Yutaka Suehiro, Takahiro Yamasaki, Hironori Yoshiyama and Isao Sakaida
Microorganisms 2019, 7(9), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7090305 - 01 Sep 2019
Cited by 24 | Viewed by 3219
Abstract
: Epstein–Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient’s number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent [...] Read more.
: Epstein–Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient’s number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent surgical resection from 2007 to 2017 in Japan and examined clinicopathological features of EBVaGC. EBV infection was detected by in situ hybridization with EBV-encoded small RNA 1(EBER-1 ISH). EBV was infected in 80 GC lesions (7.1%). Mean age was significantly lower in patients with EBVaGC than with EBV-negative GC. EBVaGC was more frequent in men than in women. EBVaGC was found twice as frequent in the upper or middle stomach as in the lower stomach. Early EBVaGC was more frequent, and submucosally invaded cases were dominant. The presence of lymphatic vessel invasion was less in EBVaGC, but frequency of lymph node metastasis was similar. Carcinoma with lymphoid stroma (CLS) was found in 3.8% (43/1132) of all lesions with 60.5% of EBV positivity. The synchronous or metachronous multiple GC was frequent in EBVaGC. We clarified clinicopathologic characteristics of EBVaGC over the past decade in Japan. EBV infection should be examined in gastric cancer cases showing these characteristics. Full article
(This article belongs to the Special Issue Recent Advances in Understanding Epstein-Barr Virus)
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12 pages, 2907 KiB  
Article
Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs
by Misako Yajima, Mamiko Miyata, Kazufumi Ikuta, Yasuhisa Hasegawa, Chitose Oneyama and Teru Kanda
Microorganisms 2019, 7(5), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7050119 - 30 Apr 2019
Cited by 4 | Viewed by 3955
Abstract
Epstein-Barr virus (EBV) genomes, particularly their latent genes, are heterogeneous among strains. The heterogeneity of EBV-encoded latent membrane protein 1 (LMP1) raises the question of whether there are functional differences between LMP1 expressed by cancer-associated EBV and that by non-cancerous strains. Here, we [...] Read more.
Epstein-Barr virus (EBV) genomes, particularly their latent genes, are heterogeneous among strains. The heterogeneity of EBV-encoded latent membrane protein 1 (LMP1) raises the question of whether there are functional differences between LMP1 expressed by cancer-associated EBV and that by non-cancerous strains. Here, we used bacterial artificial chromosome (BAC)-cloned EBV genomes retaining all virally encoded microRNA (miRNA) genes to investigate the functions of cancer-derived LMP1 in the context of the EBV genome. HEK293 cells were stably transfected with EBV-BAC clone DNAs encoding either nasopharyngeal carcinoma (NPC)-derived CAO-LMP1 (LMP1CAO) or LMP1 from a prototype B95-8 strain of EBV (LMP1B95-8). When an EBV-BAC clone DNA encoding LMP1CAO was stably transfected into HEK293 cells, it generated many more stable transformants than the control clone encoding LMP1B95-8. Furthermore, stably transfected HEK293 cells exhibited highly efficient production of progeny virus. Importantly, deletion of the clustered viral miRNA genes compromised the ability to produce progeny viruses. These results indicate that cancer-derived LMP1 and viral miRNAs together are necessary for efficient production of progeny virus, and that the resulting increase in efficiency contributes to EBV-mediated epithelial carcinogenesis. Full article
(This article belongs to the Special Issue Recent Advances in Understanding Epstein-Barr Virus)
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Review

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23 pages, 2595 KiB  
Review
Epstein–Barr Virus and Innate Immunity: Friends or Foes?
by Sonia Jangra, Kit-San Yuen, Michael George Botelho and Dong-Yan Jin
Microorganisms 2019, 7(6), 183; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7060183 - 24 Jun 2019
Cited by 45 | Viewed by 7779
Abstract
Epstein–Barr virus (EBV) successfully persists in the vast majority of adults but causes lymphoid and epithelial malignancies in a small fraction of latently infected individuals. Innate immunity is the first-line antiviral defense, which EBV has to evade in favor of its own replication [...] Read more.
Epstein–Barr virus (EBV) successfully persists in the vast majority of adults but causes lymphoid and epithelial malignancies in a small fraction of latently infected individuals. Innate immunity is the first-line antiviral defense, which EBV has to evade in favor of its own replication and infection. EBV uses multiple strategies to perturb innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like, and AIM2-like receptors as well as cyclic GMP-AMP synthase. EBV also counteracts interferon production and signaling, including TBK1-IRF3 and JAK-STAT pathways. However, activation of innate immunity also triggers pro-inflammatory response and proteolytic cleavage of caspases, both of which exhibit proviral activity under some circumstances. Pathogenic inflammation also contributes to EBV oncogenesis. EBV activates NFκB signaling and induces pro-inflammatory cytokines. Through differential modulation of the proviral and antiviral roles of caspases and other host factors at different stages of infection, EBV usurps cellular programs for death and inflammation to its own benefits. The outcome of EBV infection is governed by a delicate interplay between innate immunity and EBV. A better understanding of this interplay will instruct prevention and intervention of EBV-associated cancers. Full article
(This article belongs to the Special Issue Recent Advances in Understanding Epstein-Barr Virus)
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12 pages, 279 KiB  
Review
Extracellular Vesicles in Epstein-Barr Virus’ Life Cycle and Pathogenesis
by Mengmeng Zhao, Asuka Nanbo, Lichun Sun and Zhen Lin
Microorganisms 2019, 7(2), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7020048 - 11 Feb 2019
Cited by 35 | Viewed by 4532
Abstract
Extracellular vesicles (EVs), including exosomes and microvesicles, are evolutionarily conserved phospholidpid membrane-bound entities secreted from most eukaryotic cell types. They carry bioactive cargos such as protein and nucleic acids derived from their cells of origin. Over the past 10 years, they have been [...] Read more.
Extracellular vesicles (EVs), including exosomes and microvesicles, are evolutionarily conserved phospholidpid membrane-bound entities secreted from most eukaryotic cell types. They carry bioactive cargos such as protein and nucleic acids derived from their cells of origin. Over the past 10 years, they have been attracting increased attention in many fields of life science, representing a new route for intercellular communication. In this review article, we will discuss the current knowledge of both normal and virally modified EVs in the regulation of Epstein-Barr virus (EBV)’s life cycle and its associated pathogenesis. Full article
(This article belongs to the Special Issue Recent Advances in Understanding Epstein-Barr Virus)
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