Epstein Barr virus infection and immune defense related to HLA‐DR15: consequences for multiple sclerosis

Abstract

MS is a multifactorial disease in which a series of genetic and non‐genetic, environmental factors plays a role in its etiology. In particular, HLA class II alleles, mainly HLADRB1*15:01 (HLA‐DR15), increase the risk for this disease. Out of several environmental factors, and with regard to infections, EBV remains to be a strong candidate, and may synergize with HLA‐DR15 thus increasing the risk for MS. In this issue of the European Journal of Immunology , Zdimerova et al. present highly interesting experimental data using EBV infection in immune‐deficient mice engrafted with human immune cells, either HLA‐DR15 + or HLA‐DRB1*04:01 (HLA DR4), here after denoted as HLA‐DR15 − . As a result of EBV infection, the viral load and CD8 + cell expansion were conspicuously higher in mice engrafted with HLA‐DR15 + compared to HLA‐DR15 − mice; and myelin basic protein specific T cells emerged in mice engrafted with HLA‐DR15 bearing cells. This study sheds light on how EBV and the class II DR15 haplotype may jointly predispose and synergize in the etiology of MS.

The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis

“…Accordingly, MS risk genes are over-represented as target sites for the EBV transcription factor EBNA2, an activator of cellular and viral genes with a key role in the initial phases of EBV infection ( 340 – 342 ). A recent study in humanized animal models ( 105 ) stresses the need to investigate in more detail the interactions between specific MS susceptibility genes and immune control of EBV infection that may predispose to disease development ( 343 ). Because MHC class II functions as co-receptor for EBV entry into B cells ( 189 ), it would be important to assess if MHC class II alleles associated with increased or reduced risk for MS differentially affect the susceptibility of B cells to EBV infection.…”

“…the EBV transcription factor EBNA2, an activator of cellular and viral genes with a key role in the initial phases of EBV infection (340)(341)(342). A recent study in humanized animal models (105) stresses the need to investigate in more detail the interactions between specific MS susceptibility genes and immune control of EBV infection that may predispose to disease development (343).…”

Integration of Genetic and Immune Infiltration Insights into Data Mining of Multiple Sclerosis Pathogenesis

“…KEGG enrichment pathways in our study suggests that multiple sclerosis is closely related to environmental risk factors including viral infection, bacteria infection and certain autoimmune diseases. Epstein-Barr virus is regarded as the leading environmental risk factor 37 . And the cross-reactivity of CD4+T cells partly explained the synergistic effect between EBV infection and genetic susceptibility to multiple sclerosis 38 .…”

The Immunogenetic Basis of Idiopathic Bone Marrow Failure Syndromes: A Paradox of Similarity and Self-Presentation

“…As an example of autoimmune disorder with known self-antigenic specificities, in multiple sclerosis the link among DRB1*15:01, EBV and central nervous system antigens' molecular mimicry is well established, with indirect evidence that impaired CD4+ presentation may elicit aberrant CD8+ responses and autoantibody production. 56,57,58,59 If risk allele profiles did not impact on clinical outcomes, low divergence in class II was associated with an increased probability of malignant progression in IAA/PNH patients. This finding is in line with the idea that anti-tumor surveillance (previously shown as more efficient in highly divergent class I allele pairs) 40 could encompass also HLA class II-restricted T-cell responses.…”