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EBV (Epstein Barr Virus) has been associated with numerous autoimmune syndromes in epidemiologic studies. In this work immunoglobulin G response to EBV antigens similar to antigens from host proteins was analyzed using a laser printed microarray ( PEPperprint.com ). IgG response to overlapping peptides derived from immunologically important EBV proteins including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized. These viral proteins have domains shared with host DNA–binding proteins in the human immune response that may cross-react through “molecular mimicry” triggering antinuclear and other autoantibodies. IgG response to conserved “A/T hooks” in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA–binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. Proteomic “molecular fingerprints” of the immune response to viral proteins is relatively inexpensive and potentially useful in monitoring autoantibody production and response to therapy.

Epstein-Barr virus (also termed HHV-4, EBV), a component of the human virome or metagenome, is associated as a co-factor in many common human autoimmune diseases through epidemiologic evidence. Numerous EBV genes are functional as well as structural homologues of important immune response genes. For example, EBV-encoded BCRF1 is a functional homologue of IL-10, a critical cytokine regulator of immune tolerance. BZLF-1, an EBV-encoded transcription factor, contains regions with functional homology to both AP-1 and NF-κB DNA binding immune response regulatory factors. The author proposes a paradigm of "gene sharing" between viral- and host-encoded proteins as extension of molecular mimicry that has been largely overlooked in animal models that consider only host genomic factors rather than viral pathogens and the metagenome. Gene sharing may trigger chaotic behavior in human autoimmune disease through unstable feedback loops and perturbations of immune tolerance.