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Biomolecules
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Epstein-Barr Virus Disease Mechanisms and Stress Responses
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Epstein-Barr Virus Disease Mechanisms and Stress Responses

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 52870

Special Issue Editor

Prof. Dr. Marshall Williams

E-Mail Website
Guest Editor
1. Department of Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
2. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH 43210, USA
Interests: DNA replication and repair in eukaryotic cells and herpes viruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The virome of humans is complex and is composed of numerous virus families, including several members of the Herpesviridae. One member, Epstein–Barr virus (EBV), a gamma herpesvirus, establishes persistent infections in more than 90% of adults worldwide. EBV is the etiological agent of several human cancers, and it has also been associated with an increased risk for developing several autoimmune diseases. However, the mechanisms by which EBV may contribute to these autoimmune diseases are unknown. Likewise, little is known concerning the role that EBV may have in modulating the host immune system in asymptomatic “healthy” individuals, and how stress may alter these responses during the aging process.

This Special Issue of Biomolecules is devoted to exploring the role of how molecules produced during the reactivation/partial reactivation of EBV may contribute to modifying the host’s immune system in immunocompetent individuals, and how stress may affect these processes. The main goal is to compile articles that describe recent progress in this area.

Prof. Marshall Williams
Guest Editor

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Keywords

  • Epstein–Barr virus (EBV)
  • reactivation
  • immune modulation
  • stress
  • aging

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Related Special Issue

Published Papers (7 papers)

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Research

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8 pages, 402 KiB  
Article
Epidemiological and Liver Biomarkers Profile of Epstein-Barr Virus Infection and Its Coinfection with Cytomegalovirus in Patients with Hematological Diseases
by Lilian Ferrari de Freitas, Jean de Melo Silva, Anderson Nogueira Barbosa, Enzo Miranda Santos, Renato Pinheiro-Silva and Gemilson Soares Pontes
Biomolecules 2021, 11(8), 1151; https://doi.org/10.3390/biom11081151 - 4 Aug 2021
Cited by 4 | Viewed by 3191
Abstract
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are viruses globally distributed that have been associated with the development and prognosis of many pathologies, including hematological diseases. This study aimed to characterize the epidemiological profile of EBV infection and the infection-correlated hepatic manifestations in patients [...] Read more.
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are viruses globally distributed that have been associated with the development and prognosis of many pathologies, including hematological diseases. This study aimed to characterize the epidemiological profile of EBV infection and the infection-correlated hepatic manifestations in patients with hematological diseases of the northern Brazilian state of Amazonas. A total of 228 patients were serologically tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. The coinfection with CMV, sociodemographic and laboratory records of all patients were also assessed. The overall prevalence observed among the study population for EBV infection and EBV/CMV coinfection was 85.09% (95% CI: 0.80–0.90) and 78.51% (95% CI: 0.73–0.84), respectively. The age group 31–40 years old were more susceptible to EBV/CMV coinfection (95% CI: 1.59–93.41, p = 0.011), while young people aged 1–10 years old were less affected for both EBV infection (CI 95%; 0.66–0.91, p = 0.001) and EBV/CMV coinfection (95% CI: 0.52–0.81, p < 0.0001). High serum levels of the liver biomarker ferritin were associated with EBV infection (95% CI: 1.03–1.54, p = 0.031) and EBV/CMV coinfection (95% CI: 1.02–1.70, p = 0.038). Our findings indicated that the elevated prevalence of EBV infection is not associated with the hematological diseases or transfusion rates, but with the socioeconomic status of the study population. Also, this study suggests that the EBV infection and its coinfection with CMV are related to the increase of serum ferritin levels. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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12 pages, 295 KiB  
Article
Patterns of Genital Tract Mustelid Gammaherpesvirus 1 (Musghv-1) Reactivation Are Linked to Stressors in European Badgers (Meles Meles)
by Ming-shan Tsai, Sarah François, Chris Newman, David W. Macdonald and Christina D. Buesching
Biomolecules 2021, 11(5), 716; https://doi.org/10.3390/biom11050716 - 11 May 2021
Cited by 5 | Viewed by 2422
Abstract
Gammaherpesvirus reactivation can promote diseases or impair reproduction. Understanding reactivation patterns and associated risks of different stressors is therefore important. Nevertheless, outside the laboratory or captive environment, studies on the effects of stress on gammaherpesvirus reactivation in wild mammals are lacking. Here we [...] Read more.
Gammaherpesvirus reactivation can promote diseases or impair reproduction. Understanding reactivation patterns and associated risks of different stressors is therefore important. Nevertheless, outside the laboratory or captive environment, studies on the effects of stress on gammaherpesvirus reactivation in wild mammals are lacking. Here we used Mustelid gammaherpesvirus 1 (MusGHV-1) infection in European badgers (Meles meles) as a host–pathogen wildlife model to study the effects of a variety of demographic, physiological and environmental stressors on virus shedding in the genital tract. We collected 251 genital swabs from 150 free-ranging individuals across three seasons and screened them for the presence of MusGHV-1 DNA using PCR targeting the DNA polymerase gene. We explored possible links between MusGHV-1 DNA presence and seven variables reflecting stressors, using logistic regression analysis. The results reveal different sets of risk factors between juveniles and adults, likely reflecting primary infection and reactivation. In adults, virus shedding was more likely in badgers in poorer body condition and younger than 5 years or older than 7; while in juveniles, virus shedding is more likely in females and individuals in better body condition. However, living in social groups with more cubs was a risk factor for all badgers. We discuss possible explanations for these risk factors and their links to stress in badgers. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
12 pages, 1246 KiB  
Article
Low Vitamin D States Observed in U.S. Marines and Navy Sailors with Early Multi-Symptom Illness
by Sean R. Maloney and Paula Goolkasian
Biomolecules 2020, 10(7), 1032; https://doi.org/10.3390/biom10071032 - 11 Jul 2020
Cited by 6 | Viewed by 3097
Abstract
Research has implicated immune system inflammation as an underlying etiology of multi-symptom illnesses, and vitamin D has been shown to have a significant role in immune system function. In this retrospective review performed on the medical charts of service members who presented with [...] Read more.
Research has implicated immune system inflammation as an underlying etiology of multi-symptom illnesses, and vitamin D has been shown to have a significant role in immune system function. In this retrospective review performed on the medical charts of service members who presented with signs and symptoms of multi-symptom illnesses, we focused on serum 25(OH)D3 levels and looked for associations of vitamin D status (deficient, insufficient, and normal) with age (20–31 years versus 31–56 years) and deployment status (war zones versus other). Two groups (U.S. Marines and Navy Sailors) were sampled and both showed high incidences of below normal vitamin D levels. However, with the Marines, age-related differences in serum levels (p = 0.009) were found only among those who deployed to Iraq/Afghanistan in comparison to those in non-combat locations. The comparison within the Navy sample showed that mobilized sailors had lower 25(OH)D3 levels than the group that did not deploy (p = 0.04). In addition, 100% of the sailors who deployed had below normal levels versus only 33% in the cadre group. The data suggest that personnel returning from a war zone with signs of early multi-symptom illness should be checked for low vitamin D status. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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Review

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17 pages, 1148 KiB  
Review
The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications
by Adelaide Ohui Fierti, Michael Bright Yakass, Ernest Adjei Okertchiri, Samuel Mawuli Adadey and Osbourne Quaye
Biomolecules 2022, 12(1), 127; https://doi.org/10.3390/biom12010127 - 13 Jan 2022
Cited by 15 | Viewed by 4574
Abstract
Epstein-Barr virus (EBV) is ubiquitous and carried by approximately 90% of the world’s adult population. Several mechanisms and pathways have been proposed as to how EBV facilitates the pathogenesis and progression of malignancies, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and gastric [...] Read more.
Epstein-Barr virus (EBV) is ubiquitous and carried by approximately 90% of the world’s adult population. Several mechanisms and pathways have been proposed as to how EBV facilitates the pathogenesis and progression of malignancies, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and gastric cancers, the majority of which have been linked to viral proteins that are expressed upon infection including latent membrane proteins (LMPs) and Epstein-Barr virus nuclear antigens (EBNAs). EBV expresses microRNAs that facilitate the progression of some cancers. Mostly, EBV induces epigenetic silencing of tumor suppressor genes, degradation of tumor suppressor mRNA transcripts, post-translational modification, and inactivation of tumor suppressor proteins. This review summarizes the mechanisms by which EBV modulates different tumor suppressors at the molecular and cellular levels in associated cancers. Briefly, EBV gene products upregulate DNA methylases to induce epigenetic silencing of tumor suppressor genes via hypermethylation. MicroRNAs expressed by EBV are also involved in the direct targeting of tumor suppressor genes for degradation, and other EBV gene products directly bind to tumor suppressor proteins to inactivate them. All these processes result in downregulation and impaired function of tumor suppressors, ultimately promoting malignances. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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30 pages, 2095 KiB  
Review
Stress-Induced Epstein-Barr Virus Reactivation
by Daniel G. Sausen, Maimoona S. Bhutta, Elisa S. Gallo, Harel Dahari and Ronen Borenstein
Biomolecules 2021, 11(9), 1380; https://doi.org/10.3390/biom11091380 - 18 Sep 2021
Cited by 65 | Viewed by 16535
Abstract
Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough [...] Read more.
Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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17 pages, 1276 KiB  
Review
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!
by Maria Eugenia Ariza
Biomolecules 2021, 11(2), 185; https://doi.org/10.3390/biom11020185 - 29 Jan 2021
Cited by 38 | Viewed by 14102
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to [...] Read more.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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21 pages, 581 KiB  
Review
Early Growth Response Gene Upregulation in Epstein–Barr Virus (EBV)-Associated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
by Jonathan Kerr
Biomolecules 2020, 10(11), 1484; https://doi.org/10.3390/biom10111484 - 26 Oct 2020
Cited by 14 | Viewed by 7389
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease exhibiting a variety of symptoms and affecting multiple systems. Psychological stress and virus infection are important. Virus infection may trigger the onset, and psychological stress may reactivate latent viruses, for example, Epstein–Barr virus [...] Read more.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease exhibiting a variety of symptoms and affecting multiple systems. Psychological stress and virus infection are important. Virus infection may trigger the onset, and psychological stress may reactivate latent viruses, for example, Epstein–Barr virus (EBV). It has recently been reported that EBV induced gene 2 (EBI2) was upregulated in blood in a subset of ME/CFS patients. The purpose of this study was to determine whether the pattern of expression of early growth response (EGR) genes, important in EBV infection and which have also been found to be upregulated in blood of ME/CFS patients, paralleled that of EBI2. EGR gene upregulation was found to be closely associated with that of EBI2 in ME/CFS, providing further evidence in support of ongoing EBV reactivation in a subset of ME/CFS patients. EGR1, EGR2, and EGR3 are part of the cellular immediate early gene response and are important in EBV transcription, reactivation, and B lymphocyte transformation. EGR1 is a regulator of immune function, and is important in vascular homeostasis, psychological stress, connective tissue disease, mitochondrial function, all of which are relevant to ME/CFS. EGR2 and EGR3 are negative regulators of T lymphocytes and are important in systemic autoimmunity. Full article
(This article belongs to the Special Issue Epstein-Barr Virus Disease Mechanisms and Stress Responses)
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