<p>Multiple sclerosis (MS) is a central nervous system (CNS) disorder defined by inflammation, demyelination, and neuronal damage. Several independent studies have confirmed the prevalence of EBV infection in MS and the presence of elevated anti-EBV antibody titers in serum prior to and throughout the clinical period of MS. EBV stands out from other human-infecting viruses in that it can activate, infect, and clone the B cells and remain a latent infection inside them. The prevalence of EBV-positive B cell lymphoproliferative diseases in immunocompromised individuals demonstrates the critical significance of immune surveillance in managing EBV infection. It has also been postulated that a deficiency in EBV-specific CD8<sup>+</sup> T cell regulation predisposes to MS by allowing EBV-infected autoreactive B cells and plasma cells to concentrate in the CNS. Thus, EBV-specific T-cell therapy might have the potential to eradicate B lymphocytes infected by EBV in the CNS, preventing disease development and leading to enhanced clinical outcomes. One of the effective approaches for treating MS patients is application of EBV-specific T cells. In this method, peripheral blood mononuclear cells (PBMCs) are isolated from patients and expanded with EBV-specific antigens, resulting in antiviral cytotoxic response. This review discusses the significance of EBV in the pathogenesis of MS, the impact of disease-modifying T-cell treatments targeting EBV, therapeutic implications to target EBV in MS pathogenesis, and several novel EBV-targeting gene therapies.</p>

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Epstein–barr virus and multiple sclerosis: from pathogenesis and diagnosis to EBV-specific T cell therapy and gene-targeted therapeutics

  • Mukesh Pushkarna,
  • Ahmed Zwamel,
  • Seema Verma,
  • H. Malathi,
  • Mukhlisa Mustafayeva,
  • Harpreet Kaur,
  • Ali M. Ali Al-Nuaimi,
  • Beneen Husseen,
  • Mohammad Dahghani

摘要

Multiple sclerosis (MS) is a central nervous system (CNS) disorder defined by inflammation, demyelination, and neuronal damage. Several independent studies have confirmed the prevalence of EBV infection in MS and the presence of elevated anti-EBV antibody titers in serum prior to and throughout the clinical period of MS. EBV stands out from other human-infecting viruses in that it can activate, infect, and clone the B cells and remain a latent infection inside them. The prevalence of EBV-positive B cell lymphoproliferative diseases in immunocompromised individuals demonstrates the critical significance of immune surveillance in managing EBV infection. It has also been postulated that a deficiency in EBV-specific CD8+ T cell regulation predisposes to MS by allowing EBV-infected autoreactive B cells and plasma cells to concentrate in the CNS. Thus, EBV-specific T-cell therapy might have the potential to eradicate B lymphocytes infected by EBV in the CNS, preventing disease development and leading to enhanced clinical outcomes. One of the effective approaches for treating MS patients is application of EBV-specific T cells. In this method, peripheral blood mononuclear cells (PBMCs) are isolated from patients and expanded with EBV-specific antigens, resulting in antiviral cytotoxic response. This review discusses the significance of EBV in the pathogenesis of MS, the impact of disease-modifying T-cell treatments targeting EBV, therapeutic implications to target EBV in MS pathogenesis, and several novel EBV-targeting gene therapies.