Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L

• Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS) and other autoimmune diseases.
• Antibodies to the EBV nuclear antigen-1 (EBNA-1) are significantly increased in MS compared to healthy controls.
• Antibodies specific for EBNA-1 immunoprecipitate heterogeneous nuclear ribonucleoprotein L (HNRNPL) from proteins solubilized from human brain tissue.
• Western blots and ELISA with recombinant protein confirmed that anti-EBNA-1 IgG cross-reacts with HNRNPL.
• Anti-EBNA-1 IgG also binds the nucleus of cultured rat central nervous system cells.

Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), and antibodies to the EBV nuclear antigen-1 (EBNA-1) are consistently increased in MS patients. The hypothesis of this study is that anti-EBNA-1 antibodies cross-react with a self antigen in MS patients. We affinity purified anti-EBNA-1 antibodies from human plasma, used the anti-EBNA-1 to immunoprecipitate antigens from human brain, and identified bound antigens with mass spectrometry. Anti-EBNA-1 consistently bound heterogeneous nuclear ribonucleoprotein L (HNRNPL). We expressed both the long and short isoforms of this protein, and verified with Western blots and ELISA that the long isoform cross-reacts with EBNA-1. Immunohistochemistry demonstrated that anti-EBNA-1 bound to an antigen in the nucleus of cultured rat central nervous system cells. ELISA demonstrated the presence of antibodies to HNRNPL in the plasma of both healthy controls and MS patients, but anti-HNRNPL was not increased in MS patients. We conclude that HNRNPL is an autoantigen which cross-reacts with EBNA-1. The relevance of this autoantigen to MS and other autoimmune diseases remains to be investigated.