Molecular Mimicry Between Epstein\u2010Barr Virus and Human Herpesvirus\u20106 Proteins and Central Nervous System Proteins: Implications for T and B Cell Immunogenicity in an In Silico Study

The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance?

Herpesviruses and the microbiome

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant

BackgroundRelapsing-remitting multiple sclerosis (RRMS) involves autoimmune responses against central nervous system (CNS) self-epitopes, potentially triggered by Epstein–Barr virus (EBV) and Human Herpesvirus 6 (HHV-6) reactivation.ObjectivesTo evaluate IgG/IgA/IgM responses targeting the enteric nerve and non-myelin antigens in RRMS and investigate associations with EBV and HHV-6 markers and explore molecular mimicry between viral and host antigens.MethodsThe study included 55 RRMS patients and 63 matched healthy controls. ELISA is used to examine IgG/IgA/IgM levels against nine non-myelin self-epitopes and viral proteins (EBNA-1, dUTPases of EBV and HHV-6). Luminex immunoassay is used to quantify cytokines, chemokines, and growth factors. Disability was evaluated using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS). In-silico molecular mimicry was analyzed using UniProt, AlphaFold, PyMol, Alignmentaj, and the Immune Epitope Database (IEDB), comparing 41 viral and 36 ENS non-myelin antigens.ResultsIgG/IgA/IgM levels targeting the enteric nerve and non-myelin antigens were significantly higher in RRMS than in controls. A large part of the variance in the EDSS and MSSS scores (>60%) was explained by IgG-chondroitin sulfate, IgM-Asialo-ganglioside, and IgG-enteric nerve. There were highly significant correlations between autoimmunity to those self-antigens and either immune profiles indicating immune activation or Ig-responses to EBNA-1, and EBV/HHV-6 DUTPases. Molecular mimicry analysis confirmed the association between EBV/HHV-6 and the self-antigens by identifying shared pentapeptides, which might cause T-cell immunogenicity.ConclusionRRMS is characterized by autoimmune responses targeting the enteric nerve and non-myelin proteins. EBV and HHV-6 reactivation contribute via molecular mimicry mechanisms.Abstract Figure

Mosquito Salivary Gland Extracts Induce EBV-Infected NK Cell Oncogenesis Via CD4+ T Cells in Patients with Hypersensitivity to Mosquito Bites

BackgroundMultiple sclerosis (MS) is a neurological disease that is caused by an autoimmune response that results in the neuron’s demyelination in the central nervous system. The exact etiology of MS is not clear; however, several environmental and genetic factors are believed to participate in its initiation and development, including exposure to viruses. This study aims to investigate the association between the seropositivity and antibody titer of selected herpesviruses and MS in Jordanian MS patients.MethodIn this study, 55 MS patients and 40 age- and gender-matching apparently healthy volunteers were recruited from two main hospitals in the north of Jordan. MS patients were grouped into three types of MS based on the clinical presentation of the disease. Blood samples were collected from the participants and the IgG antibodies for human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV) nuclear antigen (EBNA), EBV viral capsid antigen (VCA) and varicella-zoster virus (VZV) were assayed by ELISA. The prevalence of seropositivity and the antibody level for each of the antibodies were compared between MS patients and controls and between the three types of MS.ResultsThere was no significant difference in the prevalence of seropositivity and in the levels of antibodies for HHV-6, EBNA and VCA between MS patients and controls and between the three types of MS. In contrast, the number of seropositive patients and the level of IgG antibodies for VZV were significantly higher in MS patients compared to the control.ConclusionThis study showed that patients with MS in the north of Jordan were more likely to be seropositive for VZV than the general population. Based on this finding, we recommend further studies to evaluate the seropositivity to VZV to be carried out in other parts of Jordan and the greater middle east to find out if there is a correlation between MS and previous infection with VZV.

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2013.53.2994 Journal of Clinical Oncology - published online before print February 3, 2014 PMID: 24493729 Targeting Epstein-Barr Virus–Associated Lymphomas Sarah NikiforowxSarah NikiforowSearch for articles by this author , Ann S. LaCascexAnn S. LaCasceSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2013.53.2994 First Page Full Text PDF Figures and Tables © 2014 by American Society of Clinical Oncology

The pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is linked to autoimmune attacks against myelin proteins, and reactivation of Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). However, the connection between viral reactivation and autoimmune biomarkers has remained unclear. To investigate immunoglobulin (Ig)G/IgA/IgM responses targeting myelin-related proteins in association with EBV and HHV-6 replication markers in RRMS. We recruited 55 patients with RRMS and 63 healthy controls and assessed IgG/IgA/IgM responses against seven myelin-related components, as well as EBV nuclear antigen 1 (EBNA-1) and deoxyuridine-triphosphate nucleotidohydrolase (dUTPases). Disability was evaluated using the Expanded Disability Status Scale (EDSS) and disease progression using the Multiple Sclerosis Severity Score (MSSS). IgG/IgA/IgM levels targeting seven myelin-related proteins were significantly higher in RRMS than in controls. IgG against myelin basic protein (MBP) (IgG-MBP), IgM-myelin-associated glycoprotein (IgM-MAG)-37-60, IgA-MBP, and IgA-myelin-oligodendrocyte-glycoprotein (IgA-MOG-31-55) distinguished RRMS from controls with a predictive accuracy of 96.6% (sensitivity=95.7%, specificity=95.2%) and an area under the ROC curve of 0.991. A large part of the variance in the EDSS (around 75%) and MSSS score (62.8%) was explained by IgG-MBP, IgM-MBP, IgA-MOG-31-55, and IgM-MAG. Part of the variance (47.4%) in the IgG/IgA/IgM responses to myelin-related proteins was explained by immune responses to EBNA and dUTPases of EBV and HHV-6. Autoimmune reactivities targeting myelin-related proteins are valuable biomarkers of RRMS and the severity and progression of RRMS. Reactivation of EBV and HHV-6 may trigger or maintain these autoimmune responses thereby impacting disease progression.

Epidemiological, biological and clinical features of HIV-related lymphomas in the era of highly active antiretroviral therapy.

Epstein-Barr virus (EBV), a human herpes virus with oncogenic potential, persists in B lymphoid tissues and is controlled by virus- specific cytotoxic T lymphocyte (CTL) surveillance. On reactivation in vitro, these CTLs recognize EBV-transformed lymphoblastoid cell lines (LCLs) in an HLA class I antigen-restricted fashion, but the viral antigens providing target epitopes for such recognition remain largely undefined. Here we have tested EBV-induced polyclonal CTL preparations from 16 virus-immune donors on appropriate fibroblast targets in which the eight EBV latent proteins normally found in LCLs (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, leader protein [LP], and latent membrane protein [LMP] 1 and 2) have been expressed individually from recombinant vaccinia virus vectors. Most donors gave multicomponent responses with two or more separate reactivities against different viral antigens. Although precise target antigen choice was clearly influenced by the donor's HLA class I type, a subset of latent proteins, namely EBNA 3A, 3B, and 3C, provided the dominant targets on a range of HLA backgrounds; thus, 15 of 16 donors gave CTL responses that contained reactivities to one or more proteins of this subset. Examples of responses to other latent proteins, namely LMP 2 and EBNA 2, were detected through specific HLA determinants, but we did not observe reactivities to EBNA 1, EBNA LP, or LMP 1. The bulk polyclonal CTL response in one donor, and components of that response in others, did not map to any of the known latent proteins, suggesting that other viral target antigens remain to be identified. This work has important implications for CTL control over EBV-positive malignancies where virus gene expression is often limited to specific subsets of latent proteins.

Background: The Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) are frequently linked to neuropsychiatric illnesses such as multiple sclerosis, depression, and chronic fatigue syndrome/myalgic encephalomyelitis. These viruses may induce autoi

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in the pericardium: A case with latency type III Epstein–Barr virus infection showing good prognosis without chemotherapy

Relevance.There is no predominant agent in the etiological structure of hemorrhagic vasculitis; instead, several factors play a role, including the activation of herpesvirus infections in the disease development. The objective of the study is determined by contradictory data and a lack of coordinated agreement regarding the etiology of hemorrhagic vasculitis. Objective: To identify the role of herpesvirus infection in the etiology of hemorrhagic vasculitis in children. Materials and methods. A cross-sectional study was conducted for 25 children aged from 2 months to 18 years with hemorrhagic vasculitis, who were on inpatient treatment at Medical Center "Children's Hospital" in Aktobe. All children underwent an enzyme-linked immunosorbent assay (ELISA) for herpesviruses: herpes simplex virus types I, II, (HSV-I, II), Epstein - Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus type 6 (HHV – 6). The received data is processed by descriptive statistics, STATISTICS 10.0. Results The herpesvirus infection was confirmed in 100% of the examined children, with herpes simplex virus I and II types being discovered in 25.9% of cases, Epstein-Barr virus in 28.46% of cases, cytomegalovirus (CMV) in 29.6% of cases, and human herpesvirus 6 (HHV-6) in 16% of cases. Moreover, they did not occur as mono-infections but rather in conjunction with the cytomegalovirus: CMV+ HSV-I, II (16 %); CMV+ EBV (8%); CMV+ HHV-6 (4%); CMV+ EBV+ HHV-6 (32%); CMV+ HSV-I, II + EBV+ HHV-6 (40%). A low concentration of herpesvirus antibodies in the blood of patients with hemorrhagic vasculitis was detected by ELISA anti-CMV IgG (11.62 U / ml), anti-HHV-6 IgG (6.82 U/ml), which indicates unstable immunity, the risk of activation of viral infection and recurrent hemorrhagic vasculitis. Conclusion.According to the study, herpesvirus infections can lead to hemorrhagic vasculitis in children. If vasculitis recurs, it is advised to check for the presence of antibodies to herpesvirus antigens; if so, an infectious neurologist's consultation and etiotropic antiviral therapy are advised. Актуальность. В этиологической структуре геморрагического васкулита нет преобладания какого-либо одного агента, а играет роль совокупность нескольких факторов, в том числе активация герпесвирусных инфекций в развитии болезни. Противоречивые данные, отсутствие единого мнения об этиологии геморрагического васкулита определяет цель исследования. Цель. Определить роль герпесвирусной инфекции в этиологии геморрагического васкулита у детей. Материалы и методы. Одномоментное поперечное исследование проведено 25 детям с диагнозом геморрагический васкулит в возрасте от 2 мес. до 18 лет, которые находились на стационарном лечении в Актюбинском Медицинском Центре «Детском стационаре» г. Актобе. Всем детям проводился иммуноферментный анализ (ИФА) на герпесвирусы: вирус простого герпеса I, II-го типов, (HSV- I, II), вирус Эпштейна – Барр (EBV), цитомегаловирус (CMV), вирус герпеса человека 6-го типа (HHV-6). Полученные данные обработаны описательной статистикой, СТАТИСТИКА 10.0. Результаты. Герпесвирусная инфекция у обследуемых детей подтверждена в 100% случаев, из них вирус простого герпеса І, ІІ-го типов выявлен в 25,9%, вирус Эпштейна – Барр – 28,46%, цитомегаловирус (CMV) – 29,6%, вирус герпеса человека 6-го типа (HHV-6) – 16% случаев. И они не встречались как моноинфекции, а в виде ассоциации с цитомегаловирусом: CMV+ HSV-I, II (16 %); CMV+ EBV (8%); CMV+ HHV-6 (4%); CMV+ EBV+ HHV-6 (32%); CMV+ HSV-I, II + EBV+ HHV-6 (40 %). Выявлено малая концентрация антител герпесвирусов в крови больных с геморрагическим васкулитом методом ИФА анти-CMV IgG (11,62 ЕД/мл), анти-HHV-6 IgG (6,82 ЕД/мл), что свидетельствует о неустойчивом иммунитете, риске активации вирусной инфекции и рецидивирующим течением геморрагического васкулита. Заключение. Исследование показало роль герпесвирусной инфекций в развитии геморрагического васкулита у детей и при рецидивирующем васкулите рекомендуется обследование на наличие антител на антигены герпесвирусов и при их положительном результате рекомендуется консультация инфекциониста о решении этиотропной противовирусной терапии. Өзектілігі. Геморрагиялық васкулиттің этиологиялық құрылымында бір агент басым болмайды, бірақ бірнеше факторлардың жиынтығы, соның ішінде аурудың дамуындағы герпесвирустық инфекциялардың белсендірілуі маңызды рөл атарады. Қарама-қайшы дәлелдер, геморрагиялық васкулиттің этиологиясы туралы бірдей тұжырымның болмауы зерттеу мақсатын анықтайды. Мақсаты. Балалардағы геморрагиялық васкулиттің этиологиясындағы герпесвирустық инфекцияның рөлін анықтау. Материалдар мен әдістер. Ақтөбе қаласының Ақтөбе Медициналық орталығы Балалар стационарында" геморрагиялық васкулитпен стационарлық ем қабылдаған 2айдан 18 жасқа дейінгі 25 балаға бір мезгілде көлденең зерттеу жүргізілді. Барлық балаларға герпесвирустарға иммуноферменттік талдау (ИФА) жүргізілді: I, II типті қарапайым герпес вирусы, (HSV-I, II), Эпштейн - Барр вирусы (EBV), цитомегаловирус (CMV), 6 типті адамның герпес вирусы (HHV–6). Алынған мәліметтер сипаттамалық статистикамен өңделді, СТАТИСТИКА 10.0. Нәтижелері. Зерттелеген балалардағы герпесвирустық инфекция 100% жағдайда расталды, оның ішінде І, ІІ типті қарапайым герпес вирусы 25,9%, Эпштейн – Барр вирусы – 28,46%, цитомегаловирус (CMV) – 29,6%, 6 типті (HHV-6) адамның герпес вирусы -16% жағдайлар анықталды. Олар моноинфекция ретінде емес, цитомегаловируспен байланыс ретінде пайда болды: CMV+ HSV-I, II (16 %); CMV+ EBV (8%); CMV+ HHV-6 (4%); CMV+ EBV+ HHV-6 (32%); CMV+ HSV-I, II + EBV+ HHV-6 (40 %).Геморрагиялық васкулитпен ауыратын науқастардың қанында герпесвирус антиденелерінің төмен концентрациясы анти-CMV IgG (11,62 бірл/мл), анти-HHV-6 IgG (6,82 бірл/мл) ИФА әдісімен анықталды, бұл тұрақсыз иммунитетті, вирустық инфекцияны белсендіру қаупін және геморрагиялық васкулиттің қайталанатын ағымын көрсетеді. Қорытынды. Зерттеу балалардағы геморрагиялық васкулиттің дамуындағы герпесвирустық инфекциялардың рөлін көрсетті және қайталанатын васкулит кезінде герпесвирус антигендеріне антиденелердің болуын тексеру ұсынылады және олардың оң нәтижесі болған кезде этиотропты вирусқа қарсы терапияны шешу үшін инфекционистпен кеңес жүргізу ұсынылады.

Epstein-Barr virus (EBV) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III), which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1). LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1) regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med/P-thr was identified as a possible risk factor for TNM stage IVB or progression to the N3 stage.

Epstein-Barr virus (EBV) is also called human herpes virus 4 (HHV-4), has detected 95% of the population and shows an asymptomatic state. EBV is etiological agent of oral hairy leukoplakia (OHL) in HIV patients. Latent membrane protein 1 ( LMP1 ), an integral EBV protein can modulate growth, differentiation, induce the expression of several cells, activation of antigens, and adhesion molecules. The LMP1 gene has been associated with OHL. Objectives : to determine the prevalence of EBV in saliva and the LMP1 gene in HIV/AIDS patients with EBV positive. Methods : A cross-sectional was conducted on HIV/AIDS patients. The presence of EBV in saliva was done by mciroarray PCR. LMP1 is examined by using nested PCR. Results : The research subjects involved 30 HIV/AIDS patients consisting 70% men and 30% women, with 50 % age group of 31-40 years old and 40% had CD4 counts <200 cells/mm 3 (40%). EBV in saliva was found in 26 out of 30 (87%) HIV patients and LMP1 was detected in 17 patients (65.38%). Conclusion : The high prevalence of EBV in saliva and the LMP1 gene may increase the risk of OHL. Early screening for EBV infection in patients with HIV/AIDS is important to reduce the risk of EBV-associated diseases.