Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

Abstract

EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host 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 using a laser-printed micro-array (PEPperprint.com). IgG response to conserved BA/T hooks^in EBVencoded 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. The author suggests that proteomic Bmolecular fingerprints^of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes.

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

“…In general, viral infections can interact with the host immune system through several mechanisms which ultimately lead to the loss of tolerance, the production of autoantibodies, the tissue deposition of immune complexes and consequent tissue damage. These are: structural or functional molecular mimicry, epitope spreading, superantigen production, bystander activation, altered apoptosis and clearance deficit, epigenetic factors, persistent or recurrent viral infection, and innate immunity activation with type I IFN production [14][15][16][17][18][19][20][21][22][23][24][25][26].…”

“…Molecular mimicry Viral antigens with structural similarity with self-antigens can be presented to and activate autoreactive T-lymphocytes. [8,9,[14][15][16][17][18] Epitope-spreading Over time, persistent viral infection elicits autoantibodies directed not only towards initial antigens but also multiple epitopes of the same antigens or even different antigens, increasing breadth of immune response.…”

Serum Peptide Immunoglobulin G Autoantibody Response in Patients with Different Central Nervous System Inflammatory Demyelinating Disorders

“…Peptide microarrays are a recently developed proteomic analysis method with a similar sensitivity to those of traditional methods [25]. Since various epitopes of viral antigens or autoantibodies often need to be analyzed simultaneously, this method is used to screen peptides related to autoimmune diseases [18,26,27]. The results of the present comprehensive peptide microarray screening of 2440 peptides selected based on previous literature [8] revealed CMV, HSV, MAG, HIF-1 alpha, and EBV-related peptides as possible candidates for discriminating CNS inflammatory demyelinating disorders.…”

Innate Immune Modulation Induced by EBV Lytic Infection Promotes Endothelial Cell Inflammation and Vascular Injury in Scleroderma

“…Importantly, a recent study has demonstrated that EBNA2, an EBV/latent protein colocalizes with autoimmune risk loci in B cells of several autoimmune diseases including SLE, strongly suggesting that EBV contributes to the origin of the genetic risk in these disorders (29). Evidences linking EBV and SSc have been also reported, since EBV latent antigens and high titers of EBV antibodies have been detected more often in SSc patients (30)(31)(32). Interestingly, it has been shown that B cells from healthy donor upon EBV transformation were able to produce anti-topoisomerase antibodies (Scl-70) strongly supporting the notion that production of autoantibodies might be directly related to EBV infection in SSc (33).…”