Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis
| العنوان: | Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis |
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| المؤلفون: | Jaap M. Middeldorp, Richard Christopher Cipian, Ute-Christiane Meier, Abbas Karimi, Ranjan Ramasamy |
| المساهمون: | AII - Infectious diseases |
| المصدر: | Frontiers in Immunology, 12:757302 Meier, U-C, Cipian, R C, Karimi, A, Ramasamy, R & Middeldorp, J M 2021, ' Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis ', Frontiers in Immunology, vol. 12, 757302 . https://doi.org/10.3389/fimmu.2021.757302Test Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Herpesvirus 4, Human, Herpesvirus 6, Human, viruses, Autoimmunity, Antigen-Antibody Complex, Pregnancy Proteins, Antibodies, Viral, medicine.disease_cause, Pathogenesis, Hypothesis and Theory, human endogenous retrovirus-W, hemic and lymphatic diseases, human herpesvirus-6, Immunology and Allergy, molecular mimicry, Myelin Sheath, B-Lymphocytes, Microglia, Coinfection, Brain, Herpesviridae Infections, Virus Latency, Molecular mimicry, medicine.anatomical_structure, Blood-Brain Barrier, Transcriptional Activation, Multiple Sclerosis, Immunology, Biology, Virus, Immune system, medicine, Epstein-Barr virus, Humans, Genetic Predisposition to Disease, Neuroinflammation, inflammatory cascade, Multiple sclerosis, Endogenous Retroviruses, Models, Immunological, Gene Products, env, RC581-607, medicine.disease, Epstein–Barr virus, Epstein-Barr Virus Nuclear Antigens, DNA, Viral, Neuroinflammatory Diseases, Virus Activation, Lymph Nodes, Immunologic diseases. Allergy |
| الوصف: | Roles for viral infections and aberrant immune responses in driving localized neuroinflammation and neurodegeneration in multiple sclerosis (MS) are the focus of intense research. Epstein-Barr virus (EBV), as a persistent and frequently reactivating virus with major immunogenic influences and a near 100% epidemiological association with MS, is considered to play a leading role in MS pathogenesis, triggering localized inflammation near or within the central nervous system (CNS). This triggering may occur directlyviaviral products (RNA and protein) and/or indirectlyviaantigenic mimicry involving B-cells, T-cells and cytokine-activated astrocytes and microglia cells damaging the myelin sheath of neurons. The genetic MS-risk factor HLA-DR2b (DRB1*1501β, DRA1*0101α) may contribute to aberrant EBV antigen-presentation and anti-EBV reactivity but also to mimicry-induced autoimmune responses characteristic of MS. A central role is proposed for inflammatory EBER1, EBV-miRNA and LMP1 containing exosomes secreted by viable reactivating EBV+ B-cells and repetitive release of EBNA1-DNA complexes from apoptotic EBV+ B-cells, forming reactive immune complexes with EBNA1-IgG and complement. This may be accompanied by cytokine- or EBV-induced expression of human endogenous retrovirus-W/-K (HERV-W/-K) elements and possibly by activation of human herpesvirus-6A (HHV-6A) in early-stage CNS lesions, each contributing to an inflammatory cascade causing the relapsing-remitting neuro-inflammatory and/or progressive features characteristic of MS. Elimination of EBV-carrying B-cells by antibody- and EBV-specific T-cell therapy may hold the promise of reducing EBV activity in the CNS, thereby limiting CNS inflammation, MS symptoms and possibly reversing disease. Other approaches targeting HHV-6 and HERV-W and limiting inflammatory kinase-signaling to treat MS are also being tested with promising results. This article presents an overview of the evidence that EBV, HHV-6, and HERV-W may have a pathogenic role in initiating and promoting MS and possible approaches to mitigate development of the disease. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06f40dd1787a0b4861f1a04bd80f87a9Test https://research.vumc.nl/en/publications/fd254190-bd3f-42b1-966a-a87b953fdb64Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....06f40dd1787a0b4861f1a04bd80f87a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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