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Pathogens
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The Impact of Epstein Barr Virus (EBV) in Clinical Practice
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The Impact of Epstein Barr Virus (EBV) in Clinical Practice

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (25 February 2024) | Viewed by 18900

Special Issue Editor

Dr. Fabio Salvatore Macaluso

E-Mail Website
Guest Editor
Department of Medicine, “Villa Sofia-Cervello” Hospital, Palermo, Italy
Interests: inflammatory bowel diseases

Special Issue Information

Dear Colleagues,

Epstein–Barr virus (EBV) is a widely disseminated human herpesvirus, which is spread by intimate contact. The majority of primary EBV infections are subclinical and unapparent, and antibodies to EBV have been demonstrated in all population groups worldwide: approximately 90 to 95 percent of adults are EBV-seropositive. As typical of members of the herpesvirus family, EBV has a latency phase in B lymphocytes, T lymphocytes, epithelial cells, and myocytes. EBV is the primary agent of infectious mononucleosis, and persists asymptomatically for life in most adults. Although reactivation disease is not a prominent issue with EBV, in contrast to other herpesviruses, EBV has been associated with aggressive lymphoproliferative disorders in transplant recipients. Furthermore, EBV can affect virtually any organ system and has been associated with such diverse disease manifestations as pneumonia, myocarditis, pancreatitis, mesenteric adenitis, myositis, glomerulonephritis, and others. It should also be noted that a large number of other manifestations have been associated with primary EBV infection including Guillain–Barré syndrome, facial nerve palsy, meningoencephalitis, and several hematologic abnormalities such as hemolytic anemia, thrombocytopenia, and aplastic anemia. Another relevant issue related to EBV infection lies in its transforming capacities, and it has been causally linked to a variety of malignancies, particularly in transplant recipients. These include Burkitt lymphoma, tumors in HIV-infected patients, Hodgkin lymphoma, nasopharyngeal and other head and neck carcinomas, and T cell lymphoma. Finally, a causative role for EBV has been investigated in several other conditions, including – but not limited to – inflammatory bowel diseases, colorectal cancer, multiple sclerosis, and many more, and its role in the condition of immunosuppression induced by drugs is still unclear.

In this exciting multifaceted context, there are still many unresolved issues that justify the development of new research on EBV as a relevant pathogen in humans. The discovery of EBV as a causative (co)-agent of some diseases, and the correct prevention or management of EBV infection, could have relevant consequences for the development of more effective therapies for certain conditions.

Dr. Fabio Salvatore Macaluso
Guest Editor

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. Pathogens 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

  • hematological disorders
  • infectious mononucleosis
  • immunosuppression
  • inflammatory bowel diseases
  • neurological disorders
  • post-transplant lymphoproliferative disorders
  • transforming virus.

Published Papers (3 papers)

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Research

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12 pages, 785 KiB  
Article
High Predictive Value of the Soluble ZEBRA Antigen (Epstein-Barr Virus Trans-Activator Zta) in Transplant Patients with PTLD
by Julien Lupo, Anne-Sophie Wielandts, Marlyse Buisson, CRYOSTEM Consortium, Mohammed Habib, Marwan Hamoudi, Patrice Morand, Frans Verduyn-Lunel, Sophie Caillard and Emmanuel Drouet
Pathogens 2022, 11(8), 928; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11080928 - 17 Aug 2022
Cited by 3 | Viewed by 1663
Abstract
The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as [...] Read more.
The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as post-transplant lymphoproliferative disease (PTLD). We studied 108 transplanted patients (17 PTLD and 91 controls), retrospectively selected from different hospitals in France and in the Netherlands. The majority of PTLD were EBV-positive diffuse large B-cell lymphomas, five patients experienced atypical PTLD forms (EBV-negative lymphomas, Hodgkin’s lymphomas, and T-cell lymphomas). Fourteen patients among the seventeen who developed a pathologically confirmed PTLD were sZEBRA positive (soluble ZEBRA, plasma level above 20 ng/mL, measured by an ELISA test). The specificity and positive predictive value (PPV) of the sZEBRA detection in plasma were 98% and 85%, respectively. Considering a positivity threshold of 20 ng/mL, the sensitivity of the sZEBRA was 82.35% and the specificity was 94.51%. The mean of the sZEBRA values in the PTLD cases were significantly higher than in the controls (p < 0.0001). The relevance of the lytic cycle and, particularly, the role of ZEBRA in lymphomagenesis is a new paradigm pertaining to the prevention and treatment strategies for PTLD. Given the high-specificity and the predictive values of this test, it now appears relevant to investigate the lytic EBV infection in transplanted patients as a prognostic biomarker. Full article
(This article belongs to the Special Issue The Impact of Epstein Barr Virus (EBV) in Clinical Practice)
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Review

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34 pages, 2150 KiB  
Review
CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases
by Manuel Ruiz-Pablos
Pathogens 2022, 11(8), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11080831 - 25 Jul 2022
Cited by 6 | Viewed by 13460
Abstract
Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 [...] Read more.
Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 domain of the β chain of MHC class II (HLA-DQ, -DR, and -DP) of the infected B lymphocyte, can block/alter the HLA class II/T-cell receptor (TCR) interaction, and confer an increased level of susceptibility towards the development of EBV-associated autoimmune diseases or cancer in genetically predisposed individuals (HLA-DRB1* and DQB1* alleles). The main developments predisposing the factors of these diseases are: EBV infection; HLA class II risk alleles; sex; and tissue that is infiltrated with EBV-latent cells, forming ectopic lymphoid structures. Therefore, there is a need to identify treatments for eliminating cells with EBV latency, because the current treatments (e.g., antivirals and rituximab) are ineffective. Full article
(This article belongs to the Special Issue The Impact of Epstein Barr Virus (EBV) in Clinical Practice)
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20 pages, 1754 KiB  
Review
Epstein-Barr Virus-Associated Carcinoma of the Larynx: A Systematic Review with Meta-Analysis
by Marcos Antonio Pereira de Lima, Álife Diêgo Lima Silva, Antônio Carlos Silva do Nascimento Filho, Thiago Lima Cordeiro, João Pedro de Souza Bezerra, Maria Aline Barroso Rocha, Sally de França Lacerda Pinheiro, Roberto Flávio Fontenelle Pinheiro Junior, Maria do Socorro Vieira Gadelha and Cláudio Gleidiston Lima da Silva
Pathogens 2021, 10(11), 1429; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111429 - 04 Nov 2021
Cited by 2 | Viewed by 1861
Abstract
Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate [...] Read more.
Over the past few decades, several publications have investigated the role of Epstein-Barr virus (EBV) in head and neck squamous cell carcinomas, and an increasing number of them have shown its presence in laryngeal tumors. The purpose of this meta-analysis was to evaluate the association of EBV with laryngeal carcinoma. The search was carried out in two databases, Scopus and PubMed, using the following terms: “Epstein-Barr virus” and “laryngeal carcinoma”. A total of 187 records were found, of which 31 were selected for meeting the inclusion and exclusion criteria. The meta-analysis yielded an overall pooled prevalence of 43.72% (95% confidence interval (CI): 34.35–53.08). Studies carried out in Europe and Eurasia had slightly higher pooled prevalence than other subgroups, while the prevalence of studies performed in developed countries was higher than in developing countries (46.37% vs. 34.02%). Furthermore, laryngeal carcinoma occurred almost three times as often among EBV-infected individuals compared to those without EBV infection (odds ratio = 2.86 (95% CI: 1.18–6.90); Begg’s test, p = 0.843 and Egger’s test, p = 0.866). Our findings support the idea that EBV is related to laryngeal carcinoma. However, further studies are needed before recognizing a definitive etiological role of EBV in the development and/or progression of laryngeal carcinomas. Full article
(This article belongs to the Special Issue The Impact of Epstein Barr Virus (EBV) in Clinical Practice)
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