Molecular signature of Epstein-Barr virus infection in multiple sclerosis brain lesions
ECTRIMS Online Library. Han M. 10/27/17; 200600; P945
Dr. May H. Han
Dr. May H. Han
Contributions
Abstract

Abstract: P945

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 12 Pathology

Several lines of evidence suggest a contribution of Epstein-Barr virus (EBV) infection in the etiology and pathogenesis of multiple sclerosis (MS). However, it is not definitively established that EBV infection is present within MS brain lesions. Thus, we sought to analyze the presence and frequency of EBV antigens in archived MS brain samples (n=17) and controls (n=9). Presence of EBV in active and chronic lesions characterized by immunohistochemistry (IHC), using antibodies against EBV antigens to differentiate lytic and latent viral infected B cells. We quantified the type and location of B cell subsets within the lesion in relation to viral antigen expression. Presence of EBV infected cells was further corroborated using a sensitive in situ hybridization assay directed against EBV encoded small RNAs (EBERs).
We report that >70% of MS samples showed higher density of latent membrane protein-1 (LMP-1) expressing EBV-infected B cells, while the majority of the samples from control brain samples showed either low (~45%) or undetectable (~20%) LMP-1 expressing B cells. In contrast, EBV early lytic protein (BZLF1) expressing B cells in the majority of the MS samples were either low or undetectable. BZLF1 expression was predominantly observed in chronic inactive lesions, suggesting an association between MS lesion type and EBV lytic cycle. Furthermore, EBER-1 positive cells were found in 85% of MS brain samples, but not detected in control samples. Although both MS and control brain samples indicated the presence of EBV infection, there were a greater percentage of MS brain samples containing CD138+ plasma cells and LMP-1 rich populations (>10 cells/mm2), suggesting that the MS brain lesion milieu may provide a favorable environment for EBV infection and B cell proliferation.
In summary, our findings demonstrate the presence of EBV infected cells in the brain of MS patients. Furthermore, although the presence of EBV-related proteins were detected in both MS and control brain samples, the significant prevalence of latent and lytic viral-associated proteins in MS brain samples, and especially in chronic inactive lesions suggest a key role of EBV during disease pathogenesis.
Disclosure:
MAM: No disclosures
NOG: No disclosures
BTA: Employment and equity ownership - Atara Biotherapeutics, Inc
EC: Consultant - Atara Biotherapeutics, Inc
RK: Research funding, Consultant, Scientific Advisory Board - Atara Biotherpeutics, Inc.; Patents licensed to Atara Biotherapeutics, Inc., Qiagen, and Cellestis, Inc. Editor-in-Chief of Clinical and Translational Immunology Journal
LS: Research funding- Atara Biotherapeutics, Consultant Atara Biotherapeutics
MH: Research funding- Atara Biotherapeutics

Abstract: P945

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 12 Pathology

Several lines of evidence suggest a contribution of Epstein-Barr virus (EBV) infection in the etiology and pathogenesis of multiple sclerosis (MS). However, it is not definitively established that EBV infection is present within MS brain lesions. Thus, we sought to analyze the presence and frequency of EBV antigens in archived MS brain samples (n=17) and controls (n=9). Presence of EBV in active and chronic lesions characterized by immunohistochemistry (IHC), using antibodies against EBV antigens to differentiate lytic and latent viral infected B cells. We quantified the type and location of B cell subsets within the lesion in relation to viral antigen expression. Presence of EBV infected cells was further corroborated using a sensitive in situ hybridization assay directed against EBV encoded small RNAs (EBERs).
We report that >70% of MS samples showed higher density of latent membrane protein-1 (LMP-1) expressing EBV-infected B cells, while the majority of the samples from control brain samples showed either low (~45%) or undetectable (~20%) LMP-1 expressing B cells. In contrast, EBV early lytic protein (BZLF1) expressing B cells in the majority of the MS samples were either low or undetectable. BZLF1 expression was predominantly observed in chronic inactive lesions, suggesting an association between MS lesion type and EBV lytic cycle. Furthermore, EBER-1 positive cells were found in 85% of MS brain samples, but not detected in control samples. Although both MS and control brain samples indicated the presence of EBV infection, there were a greater percentage of MS brain samples containing CD138+ plasma cells and LMP-1 rich populations (>10 cells/mm2), suggesting that the MS brain lesion milieu may provide a favorable environment for EBV infection and B cell proliferation.
In summary, our findings demonstrate the presence of EBV infected cells in the brain of MS patients. Furthermore, although the presence of EBV-related proteins were detected in both MS and control brain samples, the significant prevalence of latent and lytic viral-associated proteins in MS brain samples, and especially in chronic inactive lesions suggest a key role of EBV during disease pathogenesis.
Disclosure:
MAM: No disclosures
NOG: No disclosures
BTA: Employment and equity ownership - Atara Biotherapeutics, Inc
EC: Consultant - Atara Biotherapeutics, Inc
RK: Research funding, Consultant, Scientific Advisory Board - Atara Biotherpeutics, Inc.; Patents licensed to Atara Biotherapeutics, Inc., Qiagen, and Cellestis, Inc. Editor-in-Chief of Clinical and Translational Immunology Journal
LS: Research funding- Atara Biotherapeutics, Consultant Atara Biotherapeutics
MH: Research funding- Atara Biotherapeutics

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