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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear
J William Lindsey1, Samantha L deGannes1, Kimberly A Pate1
1Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
Abstract:
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.
Insights
Antibodies to Epstein-Barr virus nuclear antigen-1 (EBNA-1) in multiple sclerosis patients cross-react with a human protein called heterogeneous nuclear ribonucleoprotein L (HNRNPL). This cross-reactivity suggests HNRNPL may be an autoantigen relevant to MS.
Area of Science:
- Neuroimmunology
- Virology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) infection is linked to multiple sclerosis (MS).
- Elevated antibodies to EBV nuclear antigen-1 (EBNA-1) are common in MS patients, suggesting a potential role in disease pathogenesis.
- A key hypothesis is that anti-EBNA-1 antibodies may cross-react with self-antigens in the central nervous system.
Purpose of the Study:
- To investigate the potential cross-reactivity between anti-EBNA-1 antibodies and self-antigens in individuals with multiple sclerosis.
- To identify specific self-antigens that bind to anti-EBNA-1 antibodies purified from MS patient plasma.
Main Methods:
- Affinity purification of anti-EBNA-1 antibodies from human plasma.
- Immunoprecipitation of antigens from human brain tissue using purified anti-EBNA-1 antibodies.
- Mass spectrometry to identify bound antigens.
- Western blot and ELISA to verify cross-reactivity with specific protein isoforms.
- Immunohistochemistry to localize the antigen in neural cells.
Main Results:
- Anti-EBNA-1 antibodies consistently bound to heterogeneous nuclear ribonucleoprotein L (HNRNPL).
- The long isoform of HNRNPL was confirmed to cross-react with EBNA-1.
- Immunohistochemistry showed anti-EBNA-1 binding to an antigen within the nucleus of cultured rat CNS cells.
- Antibodies to HNRNPL were present in both healthy controls and MS patients, with no significant increase observed in MS patients.
Conclusions:
- Heterogeneous nuclear ribonucleoprotein L (HNRNPL) is identified as an autoantigen that cross-reacts with EBNA-1.
- This cross-reactivity suggests a potential mechanism linking EBV infection to autoimmune responses in MS.
- Further research is needed to determine the specific role of HNRNPL as an autoantigen in MS and other autoimmune diseases.
