The are some people that believe that MS is caused by EBV and there are some of then that think there are EBVvariants that cause MS. Now i can buy the former view but as to the latter view I say where is the evidence, you just have to read to see that people have looked for this and they have yet to support this view. I also ask why do you need to have this view…the major histocompatibility complex (transplantation antigen) that we express can help create this tissue target specificity. without the need for variants to come into the picture
Veroni C, Carbone F, Ricci D, Proietti S, Romano S, Buscarinu MC, Rizzo F, Marrone A, Micillo T, Perna F, Garziano F, Guerrera G, Valentino P, Meloni C, Bellucci G, Bertolotto A, Battistini L, Ristori G, Centonze D, Matarese G, Coccia EM, Salvetti M, Severa M, Mechelli R. Multiple sclerosis-associated EBNA2 variants influence the response to peginterferon beta-1a therapy. J Autoimmun. 2026 Feb 12;159:103533.Â
Background: Strong evidence links Epstein-Barr virus (EBV) infection to Multiple Sclerosis (MS). Peginterferon beta-1a (peg-IFN), currently the most used interferon formulation among first-line treatments in MS, displays immunomodulatory, anti-inflammatory, and antiviral properties and remains also an important therapeutic option in conditions such as pregnancy, lactation and aging patients.
Objectives: In this study we evaluated the ability of peg-IFN to restore a homeostatic EBV-host interaction in MS by regulating antiviral and immunometabolic responses.
Methods: In people with MS (pwMS), peripheral blood mononuclear cells (PBMCs) were analyzed before (T0) and after six months (T6mos) of peg-IFN administration: IFN-stimulated gene (ISG) levels, EBV DNA load, Epstein-Barr nuclear antigen 2 (EBNA2) allele distribution, and T-lymphocyte phenotyping with glycolytic metabolism were assessed.
Results: Peg-IFN increased ISG transcription and glycolysis in CD4+ T lymphocytes, and reduced EBV DNA load without altering EBNA2 allele distribution. Notably, ISG expression increase at T6mos in pwMS infected by the non-risk 1.3B EBNA2 allele, correlating with a better long-term response to peg-IFN after 2-years. Lower T-cell glycolytic capacity at T0 predicted higher peg-IFN responsiveness in pwMS carrying the 1.3B allele, suggesting that EBNA2 variants might be predictive of response to peg-IFN.
Conclusion: Here, we found that infection with MS-associated EBNA2 variants might be involved in the clinical response to peg-IFN therapy. The predictive model developed, which integrates immunological and viral parameters, may help clinicians in a finer selection of first-line therapies tailored to patient profiles, supporting personalized medicine approaches.
Source: multiple-sclerosis-research.org