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9 pages, 1550 KiB

Open AccessCommunication

Establishment of Epstein–Barr Virus (EBV) Latent Gene-Expressing T-Cell Lines with an Expression Vector Harboring EBV Nuclear Antigen 1

by Hiroyuki Kanno, Tomohiro Osada and Ayako Tateishi

Microorganisms 2023, 11(11), 2624; https://doi.org/10.3390/microorganisms11112624 - 25 Oct 2023

Cited by 1 | Viewed by 1046

Abstract

Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is characterized by chronic or recurrent infectious mononucleosis-like symptoms and is associated with EBV-associated T/natural killer (NK)-cell lymphoproliferative disorders, which frequently lead to the development of life-threatening complications, such as virus-associated hemophagocytic syndrome and EBV-positive apparent [...] Read more.

Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is characterized by chronic or recurrent infectious mononucleosis-like symptoms and is associated with EBV-associated T/natural killer (NK)-cell lymphoproliferative disorders, which frequently lead to the development of life-threatening complications, such as virus-associated hemophagocytic syndrome and EBV-positive apparent leukemia/lymphoma mainly in T- and NK-cell lineages. In order to clarify the EBV genes responsible for the diseases, we introduced the plasmid coding sequences of EBV-encoded small RNAs (EBERs) and/or latent membrane protein (LMP) 1 into human T-lymphocyte virus-I-negative human T-cell lines using a gene expression vector harboring EBV nuclear antigen 1, established the G418-resistant transformants of five T-cell lines, and quantitatively examined the expression of EBERs and LMP1 using real-time reverse transcriptase–polymerase chain reaction. The expression levels of EBERs in T-cell transformants with EBER DNA paralleled those in EBV-positive human T- and NK-cell lines, SNTK cells. The expression of LMP1 mRNA varied in SNTK cells and in human T-cell transformants, and the expression of LMP1 mRNA in T-cell lines expressing both EBERs and LMP1 was much lower than that in the same cell line expressing LMP1 mRNA alone. The currently employed gene expression system and currently obtained transformants may be useful for the analyses of the pathophysiology of CAEBV and EBV-positive T/NK-cell lymphoproliferative disorders. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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6 pages, 750 KiB

Open AccessCommunication

Endoscopic Diagnosis and Therapy for Epstein–Barr Virus-Associated Gastric Cancer

by Hideo Yanai, Junko Fujiwara, Eiichiro Toyama, Hiroshi Okuda, Osamu Miura, Seiji Kaino and Jun Nishikawa

Microorganisms 2023, 11(11), 2619; https://doi.org/10.3390/microorganisms11112619 - 24 Oct 2023

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Abstract

Epstein-Barr-virus-associated gastric cancer (EBVaGC) represents almost 7% of all GC and is a distinct subtype of GC with extreme DNA hypermethylation. EBVaGC is a tumor-infiltrating lymphocyte-rich tumor with little lymph-node metastasis in its early stage and with a relatively favorable prognosis in its [...] Read more.

Epstein-Barr-virus-associated gastric cancer (EBVaGC) represents almost 7% of all GC and is a distinct subtype of GC with extreme DNA hypermethylation. EBVaGC is a tumor-infiltrating lymphocyte-rich tumor with little lymph-node metastasis in its early stage and with a relatively favorable prognosis in its advanced stage. Using upper gastrointestinal endoscopy, we recognize EBVaGC as a mainly depressed type with SMT-like protrusion in the upper part of the stomach near the gastric mucosal atrophic border or remnant stomach. The EBVaGC recognition rate of 21.4% with the endoscopic motif is not high, and further progress in endoscopic diagnosis of EBVaGC is needed. As less invasive endoscopic therapy, the extension of the criteria of endoscopic submucosal dissection (ESD) for early EBVaGC with little lymph-node metastasis should be discussed. Endoscopic diagnosis of EBVaGC may be relevant for the selection of patients who could benefit from endoscopic treatment or chemotherapy. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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13 pages, 794 KiB

Open AccessArticle

Detection and Quantification of the Epstein-Barr Virus in Lymphoma Patients from Ethiopia: Molecular and Serological Approaches

by Seifegebriel Teshome, Kidist Zealiyas, Abdulaziz Abubeker, Fisihatsion Tadesse, Jayalakshmi Balakrishna, Christoph Weigel, Tamrat Abebe, Elshafa Hassan Ahmed and Robert A. Baiocchi

Microorganisms 2023, 11(10), 2606; https://doi.org/10.3390/microorganisms11102606 - 22 Oct 2023

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Abstract

The Epstein-Barr virus (EBV) is a known oncogenic virus associated with various lymphoma subtypes throughout the world. However, there is a lack of information regarding EBV prevalence in lymphoma patients, specifically in Ethiopia. This study aimed to investigate the presence of the EBV [...] Read more.

The Epstein-Barr virus (EBV) is a known oncogenic virus associated with various lymphoma subtypes throughout the world. However, there is a lack of information regarding EBV prevalence in lymphoma patients, specifically in Ethiopia. This study aimed to investigate the presence of the EBV and determine its viral load in lymphoma patients from Ethiopia using molecular and serological approaches. Lymphoma patient samples were collected from the Ethiopian population. DNA and serum samples were extracted and subjected to molecular detection methods, including quantitative polymerase chain reaction (qPCR) analysis targeting the EBNA1 gene. Serological analyses were performed using an enzyme-linked immunosorbent assay (ELISA) to detect EBV viral capsid antigen IgG antibodies. EBV DNA was detected in 99% of lymphoma patients using qPCR, and serological analyses showed EBV presence in 96% of cases. A high EBV viral load (>10,000 EBV copies/mL) was observed in 56.3% of patients. The presence of high EBV viral loads was observed in 59.3% of HL patients and 54.8% of NHL patients. This study provides important insights into the prevalence and viral load of the EBV among lymphoma patients in Ethiopia. The findings contribute to the limited knowledge in this area and can serve as a foundation for future research. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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16 pages, 3083 KiB

Open AccessArticle

Markers of Epstein–Barr Virus Infection in Association with the Onset and Poor Control of Rheumatoid Arthritis: A Prospective Cohort Study

by Danijela Miljanovic, Andja Cirkovic, Ivica Jermic, Milica Basaric, Ivana Lazarevic, Milka Grk, Rada Miskovic, Aleksa Despotovic and Ana Banko

Microorganisms 2023, 11(8), 1958; https://doi.org/10.3390/microorganisms11081958 - 31 Jul 2023

Cited by 1 | Viewed by 1192

Abstract

Although the connection between Epstein–Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 [...] Read more.

Although the connection between Epstein–Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein–Barr nuclear antigen 1—EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen—CA) and anti-EBV-EA(D)-IgG (early antigen—EA) antibodies than controls (p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify “who is the chicken and who is the egg” in this EBV–RA relationship. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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Review

Jump to: Research

11 pages, 1157 KiB

Open AccessReview

Current Insights into the Maturation of Epstein–Barr Virus Particles

by Asuka Nanbo

Microorganisms 2024, 12(4), 806; https://doi.org/10.3390/microorganisms12040806 - 17 Apr 2024

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Abstract

The three subfamilies of herpesviruses (alphaherpesviruses, betaherpesviruses, and gammaherpesviruses) appear to share a unique mechanism for the maturation and egress of virions, mediated by several budding and fusion processes of various organelle membranes during replication, which prevents cellular membrane disruption. Newly synthesized viral [...] Read more.

The three subfamilies of herpesviruses (alphaherpesviruses, betaherpesviruses, and gammaherpesviruses) appear to share a unique mechanism for the maturation and egress of virions, mediated by several budding and fusion processes of various organelle membranes during replication, which prevents cellular membrane disruption. Newly synthesized viral DNA is packaged into capsids within the nucleus, which are subsequently released into the cytoplasm via sequential fusion (primary envelopment) and budding through the inner and outer nuclear membranes. Maturation concludes with tegumentation and the secondary envelopment of nucleocapsids, which are mediated by budding into various cell organelles. Intracellular compartments containing mature virions are transported to the plasma membrane via host vesicular trafficking machinery, where they fuse with the plasma membrane to extracellularly release mature virions. The entire process of viral maturation is orchestrated by sequential interactions between viral proteins and intracellular membranes. Compared with other herpesvirus subfamilies, the mechanisms of gammaherpesvirus maturation and egress remain poorly understood. This review summarizes the major findings, including recently updated information of the molecular mechanism underlying the maturation and egress process of the Epstein–Barr virus, a ubiquitous human gammaherpesvirus subfamily member that infects most of the population worldwide and is associated with a number of human malignancies. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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16 pages, 873 KiB

Open AccessReview

Recent Advances in Assessing the Clinical Implications of Epstein-Barr Virus Infection and Their Application to the Diagnosis and Treatment of Nasopharyngeal Carcinoma

by Tomokazu Yoshizaki, Satoru Kondo, Hirotomo Dochi, Eiji Kobayashi, Harue Mizokami, Shigetaka Komura and Kazuhira Endo

Microorganisms 2024, 12(1), 14; https://doi.org/10.3390/microorganisms12010014 (registering DOI) - 20 Dec 2023

Viewed by 1256

Abstract

Reports about the oncogenic mechanisms underlying nasopharyngeal carcinoma (NPC) have been accumulating since the discovery of Epstein-Barr virus (EBV) in NPC cells. EBV is the primary causative agent of NPC. EBV–host and tumor–immune system interactions underlie the unique representative pathology of NPC, which [...] Read more.

Reports about the oncogenic mechanisms underlying nasopharyngeal carcinoma (NPC) have been accumulating since the discovery of Epstein-Barr virus (EBV) in NPC cells. EBV is the primary causative agent of NPC. EBV–host and tumor–immune system interactions underlie the unique representative pathology of NPC, which is an undifferentiated cancer cell with extensive lymphocyte infiltration. Recent advances in the understanding of immune evasion and checkpoints have changed the treatment of NPC in clinical settings. The main EBV genes involved in NPC are LMP1, which is the primary EBV oncogene, and BZLF1, which induces the lytic phase of EBV. These two multifunctional genes affect host cell behavior, including the tumor–immune microenvironment and EBV behavior. Latent infections, elevated concentrations of the anti-EBV antibody and plasma EBV DNA have been used as biomarkers of EBV-associated NPC. The massive infiltration of lymphocytes in the stroma suggests the immunogenic characteristics of NPC as a virus-infected tumor and, at the same time, also indicates the presence of a sophisticated immunosuppressive system within NPC tumors. In fact, immune checkpoint inhibitors have shown promise in improving the prognosis of NPC patients with recurrent and metastatic disease. However, patients with advanced NPC still require invasive treatments. Therefore, there is a pressing need to develop an effective screening system for early-stage detection of NPC in patients. Various modalities, such as nasopharyngeal cytology, cell-free DNA methylation, and deep learning-assisted nasopharyngeal endoscopy for screening and diagnosis, have been introduced. Each modality has its advantages and disadvantages. A reciprocal combination of these modalities will improve screening and early diagnosis of NPC. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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12 pages, 1252 KiB

Open AccessReview

The Research Progress on Immortalization of Human B Cells

by Huiting Xu, Xinxin Xiang, Weizhe Ding, Wei Dong and Yihong Hu

Microorganisms 2023, 11(12), 2936; https://doi.org/10.3390/microorganisms11122936 - 7 Dec 2023

Viewed by 1947

Abstract

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include [...] Read more.

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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15 pages, 957 KiB

Open AccessReview

Epstein-Barr Virus Encephalitis: A Review of Case Reports from the Last 25 Years

by Marine Peuchmaur, Joris Voisin, Mathieu Vaillant, Aurélie Truffot, Julien Lupo, Patrice Morand, Marion Le Maréchal and Raphaele Germi

Microorganisms 2023, 11(12), 2825; https://doi.org/10.3390/microorganisms11122825 - 21 Nov 2023

Viewed by 3012

Abstract

Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature [...] Read more.

Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature search identified 97 EBV encephalitis cases. In the selected cases, EBV-related neurological disorders manifested as lymphocytic pleocytosis in the cerebrospinal fluid (CSF) with moderate hyperproteinorachia. The EBV PCR test was positive in 87% of the CSF samples, with wide-ranging viral loads. When encephalitis occurred in the context of past EBV infections, all of the EBV PCR tests on CSF samples were positive. On the contrary, negative EBV PCR tests on CSF samples occurred only in the context of primary infections. EBV PCR was rarely carried out on blood samples, contributing minimally to the diagnosis. For the treatment of EBV encephalitis, Aciclovir was used alone in 29% of cases, and in association with other drugs in 40% of cases. Ganciclovir (30%), corticoids (52%), and immunoglobulins (15%) were mainly used in association with other drugs. Cerebral imaging was abnormal in 69% of cases, mostly in the cerebellum and basal ganglia. This work highlights that the EBV PCR test on CSF samples is currently the main laboratory diagnostic test to diagnose EBV encephalitis. This diagnostic test is useful; however, it is imperfect. New complementary diagnostic tools, approved treatments, and standardized practices could improve patient management. Full article

(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases 2.0)

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